A Dissertation on
EARLY WARNING SCORE IN FEBRILE THROMBOCYTOPENIA
Dissertation Submitted to
THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY CHENNAI - 600 032
With partial fulfillment of the regulations for the award of the degree of M.D. GENERAL MEDICINE
BRANCH-I
COIMBATORE MEDICAL COLLEGE, COIMBATORE
MAY 2019
DECLARATION
I Solemnly declare that the dissertation titled “EARLY WARNING SCORE IN FEBRILE THROMBOCYTOPENIA” was done by me from JULY 2017 to JUNE 2018,at Coimbatore Medical College, during the academic year from 2016 to 2019, under the guidance and supervision of Prof. Dr K.SIVAKUMAR M.D., Professor, Department of General Medicine, Coimbatore Medical College and Hospital, Coimbatore.
This dissertation is submitted to The Tamilnadu Dr.M.G.R. Medical University towards the partial fulfilment of the requirement for the award of MD degree in General Medicine (Branch 1)
Place: Coimbatore Dr.C.VIGNESH.
Date:
CERTIFICATE - I
Certified that this dissertation in “EARLY WARNING SCORE IN FEBRILE THROMBOCYTOPENIA” is the bonafide dissertation done by Dr.C.Vignesh and submitted in partial fulfilment of the requirements for the Degree of M.D. GENERAL MEDICINE Branch I during the academic year 2016-2019 of The Tamilnadu Dr. M.G.R. Medical University, Chennai.
Prof. Dr. K. Sivakumar M.D
Date: Professor and Guide
Department of General Medicine Coimbatore Medical College
Prof. Dr. Kumar Natarajan M.D., Date: Professor & Head of Department Department of General Medicine
Coimbatore Medical College
Date: Prof. Dr. B. Asokan M.S., M.Ch., (Plastic Surgery)
Dean
Coimbatore Medical College Coimbatore
CERTIFICATE – II
This is to certify that this dissertation work titled “EARLY WARNING SCORE IN FEBRILE THROMBOCYTOPENIA” of the candidate Dr.C.VIGNESH with registration Number 201611317 for the award of M.D in the branch of General Medicine. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion 82 pages and result shows 3% (Three Percentage) percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal
ACKNOWLEDGEMENT
I wish to express my sincere thanks to our respected Dean Dr.B.ASOKAN M.S.,MCh.,(Plastic Surgery)for having allowed me to conduct this study in our hospital.
I express my heartfelt thanks and deep gratitude to the Head of the Department of General Medicine Prof. Dr.KUMAR NATARAJAN M.D., for the valuable help and cooperation and allowing me to use institutional facilities.
I sincerely thank Prof. Dr.K.SIVAKUMAR M.D., for his generous help and guidance in the course of the study.
I sincerely thank all my Asst. Professors Dr.K.SIVAKUMAR M.D., and Dr.S.BALAJI M.D., DTCD., for their guidance and help.
My sincere thanks to Prof. Dr. LALITHA M.D., HOD, Department of Pathology, for their valuable help and cooperation and allowing me to use institutional facilities.
My sincere thanks to Prof. Dr. MANIMEGALAI M.D., HOD, Department of Biochemistry, for their valuable help and cooperation and allowing me to use institutional facilities.
I am very thankful to all my friends and post-graduate colleagues for their whole hearted support and companionship during my studies.
I am very thankful to my lovable PARENTS for their moral and financial support to complete my study.
I thank all my PATIENTS, who formed the backbone of this study without whom this study would not have been possible.
Lastly, I am ever grateful to the ALMIGHTY GOD for always showering His blessings on me and my family.
Dr. C. Vignesh
LIST OF ABBREVIATIONS USED
IL - Interleukin
IFN - Interferon
TNF - Tumor Necrosis Factor PGE2 - Prostagladin E2
cAMP - Cyclic Adenosine Monophosphate ICAM - Intercellular Adhesion Molecule VCAM - Vascular cell Adhesion Molecule
DENV - Dengue Virus
PT - Prothrombin Time
APTT - Activated Partial Thromboplastin Time CNS - Central Nervous System
RS - Respiratory System
ESR - Erythrocyte Sedimentation Rate
TABLE OF CONTENTS
SL.NO TITLES PAGE.NO
1 INTRODUCTION 1
2 AIMS AND OBJECTIVES 3
3 REVIEW OF LITERATURE 4
4 MATERIALS AND METHODS 34
5 OBSERVATION AND RESULTS 38
6 DISCUSSION 73
7 SUMMARY 78
8 CONCLUSION 82
9 BIBLIOGRAPHY 83
10 ANNEXURES
PROFORMA 89
CONSENT FORM 91
MASTER CHART 95
LIST OF TABLES
SI NO TITLE PAGE NO
1 AGE DISTRIBUTION 39
2 AGE VS OUTCOME 40
3 SEX DISTRIBUTION 41
4 SEX VS OUTCOME 42
5 PULSE RATE 43
6 PULSE RATE VS OUTCOME 44
7 SYSTOLIC BLOOD PRESSURE 45
8 SYSTOLIC BLOOD PRESSURE VS OUTCOME 46
9 TEMPERATURE 47
10 TEMPERATURE VS OUTCOME 48
11 OXYGEN SATURATION 49
12 OXYGEN SATURATION VS OUTCOME 50
13 RESPIRATORY RATE 51
14 RESPIRATORY RATE VS OUTCOME 52
15 HAEMATOCRIT 53
16 HAEMATOCRIT VS OUTCOME 54
17 PLATELET COUNT 55
18 PLATELET COUNT VS OUTCOME 56
19 CNS INVOLVEMENT 57
20 CNS INVOLVEMENT VS OUTCOME 58
21 RESPIRATORY SYSTEM INVOLVEMENT 59 22 RS INVOLVEMENT VS OUTCOME 60
23 HAEMATOLOGICAL INVOLVEMENT 61
24 HAEMATOLOGICAL INVOLVEMENT VS
OUTCOME
62
25 RENAL INVOLVEMENT 63
26 RENAL INVOLVEMENT VS OUTCOME 64
27 HEPATIC INVOLVEMENT 65
28 HEPATIC INVOLVEMENT VS OUTCOME 66
29 BLEEDING MANIFESTATIONS 67
30 BLEEDING MANIFESTATIONS VS OUTCOME 68
31 PLATELET TRANSFUSION 69
32 PLATELET TRANSFUSION VS OUTCOME 70
33 OUTCOME IN TERMS OF MORTALITY 71
LIST OF CHARTS
SI NO TITLE PAGE NO
1 AGE DISTRIBUTION 39
2 AGE VS OUTCOME 40
3 SEX DISTRIBUTION 41
4 SEX VS OUTCOME 42
5 PULSE RATE 43
6 PULSE RATE VS OUTCOME 44
7 SYSTOLIC BLOOD PRESSURE 45
8 SYSTOLIC BLOOD PRESSURE VS OUTCOME 46
9 TEMPERATURE 47
10 TEMPERATURE VS OUTCOME 48
11 OXYGEN SATURATION 49
12 OXYGEN SATURATION VS OUTCOME 50
13 RESPIRATORY RATE 51
14 RESPIRATORY RATE VS OUTCOME 52
15 HAEMATOCRIT 53
16 HAEMATOCRIT VS OUTCOME 54
17 PLATELET COUNT 55
18 PLATELET COUNT VS OUTCOME 56
19 CNS INVOLVEMENT 57
20 CNS INVOLVEMENT VS OUTCOME 58
21 RESPIRATORY SYSTEM INVOLVEMENT 59
22 RS INVOLVEMENT VS OUTCOME 60
23 HAEMATOLOGICAL INVOLVEMENT 61
24 HAEMATOLOGICAL INVOLVEMENT VS
OUTCOME
62
25 RENAL INVOLVEMENT 63
26 RENAL INVOLVEMENT VS OUTCOME 64
27 HEPATIC INVOLVEMENT 65
28 HEPATIC INVOLVEMENT VS OUTCOME 66
29 BLEEDING MANIFESTATIONS 67
30 BLEEDING MANIFESTATIONS VS OUTCOME 68
31 PLATELET TRANSFUSION 69
32 PLATELET TRANSFUSION VS OUTCOME 70
33 OUTCOME IN TERMS OF MORTALITY 71
1
INTRODUCTION
Fever is one of the most important and common symptom of various diseases and manifestation of systemic illness. Fever is also known as
“Pyrexia”, from Greek “ pyretus” – which means fire. The word“ Febrile” is derived the Latin word ”Febris” - which means fever. According to studies of healthy individuals 18-40 years of age, the mean oral temperature is 36.8 ± 0.4 degC ,with low levels at 6.am and higher levels at 4-6 p.m. Rectal temperatures are generally 0.4 deg c (0.7deg F) higher than oral readings. Fever is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamus set point.
In light of various studies , morning temperature of > 37.2 (98.9) or an evening temperature of 37.7 (99.9) would define a fever. A fever of >41.5 deg C (>106.7deg F) is called hyperpyrexia . This extraordinary high fever can develop in patients with severe infections but most commonly occur in CNS hemorrhages.
Fever mostly occurs with other signs and symptoms, rarely it presents as single symptom. Most of the times it is associated with thrombocytopenia. The normal platelet count is 1,50,000 to 4,50,000 cells/cu.mm. Thrombocytopenia results from either increased sequestration or destruction of platelets , decreased production. The causes of thrombocytopenia varies from idiopathic, autoimmune, infections to malignancies. Most common cause for patients
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presenting with acute febrile -illness and thrombocytopenia is usually of infectious etiology like malaria, dengue , typhoid and leptospirosis. These infectious diseases are more common in tropical countries like India.
In recent years fever with thrombocytopenia is common clinical presentation. It causes significant morbidity in the form of bleeding manifestation, hemodynamic instability and sometimes leads to mortality. This causes increased anxiety among patients and their relatives. Literature shows many studies regarding fever with thrombocytopenia, its manifestations and its clinicopathological profiles. But there are very few studies regarding the early predictors regarding its morbidity and mortality.
Hence in this study the patients with fever with thrombocytopenia were clinically and hematologically assessed and an early warning score is to derived for the effective and intensive care for these patients to decrease its morbidity and mortality of the patients. It also helps the primary and secondary care centers to predict the serious condition of the illness and refer to higher and intensive care centers for the betterment of patients.
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AIM OF OUR STUDY
1) To study about mortality indicators in febrile thrombocytopenic patients.
2) To develop a scoring system in fever with thrombocytopenia patients for management regarding treatment and further interventions.
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REVIEW OF LITERATURE
Pathophysiology of fever:
The febrile response to a disease or illness is a complex physiologic reaction that involves various chemical mediators, hormonal and immunologic systems. Approaches to treatment and interventions can be formulated by understanding the basic mechanisms of the diseases or systemic illness that causes fever.
Pyrogens1
The term pyrogen( Greek pyro, “fire”) is used to describe any substance that causes fever. Exogenous pyrogens are derived from outside the patient;
most are microbial products, microbial toxins, or whole microorganisms (including viruses). The classic example of an exogenous pyrogen is the lipopolysaccharide (endotoxin) produced by all gram-negative bacteria.
Pyrogenic products of gram-positive organisms include the enterotoxins of staphylococcus aureus and the groups A and B streptococcal toxins, also called super antigens. One staphylococcal toxin of clinical importance is that associated with isolates of staphylococcus aureus from patients with toxic shock syndrome. These products of staphylococci and streptococci cause fever in experimental animals when injected intravenously at concentrations of 1-10 mcg/kg. Endotoxin is a highly pyrogenic molecule in humans: when injected
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intravenously into volunteers, a dose 2-3 ng/kg produces fever, leukocytes, acute-phase proteins, and generalized symptoms of malaise.
Pyrogenic cytokines:
Cytokines are small proteins (molecular mass, 10,000 -20,000 Da) that regulate immune, inflammatory, and hematopoietic processes. For example, the elevated leukocytosis seen in several infections with an absolute neutrophilia is attributable to the cytokines interleukin(IL) 1 and interleukin 6. Some cytokines also cause fever; formerly referred to as endogenous pyrogens, they are now called pyrogenic cytokines. The pyrogenic cytokines include interleukin 1,IL-6, tumour necrosis factor and cilliaryneurotropic factor, a member of the IL-6 family. Interferons (IFNs), particularly IFN-alpha, also are pyrogenic cytokines; fever is a prominent side effect of IFN-alpha used in the treatment of hepatitis. Each pyrogenic cytokine is encoded by a separate gene, and each has been shown to cause fever in laboratory animals and in humans.
When injected into humans at lose doses(10-100 ng/kg), IL-1 and TNF produce fever; incontrast, for IL-6, a dose of 1-10 mcg/kg is required for fever production.
A wide spectrum of bacterial and fungal products induce the synthesis and release of pyrogenic cytokines. However, fever can be a manifestation of disease in the absence of microbial infection. For example, inflammatory processes, trauma, tissue necrosis and antigen-antibody complexes induce the
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production of IL-1, TNF and/or IL-6; individually or in combination, these cytokines trigger the hypothalamus to raise the set point to febrile levels.
Elevation of the hypothalamic set point by cytokines
During fever, levels of prostaglandin E2 (PGE2) are elevated in hypothalamic tissue and the third cerebral ventricle. The concentrations of PGE2 are highest near the circumventricular vascular organs (organum vasculosum of lamina terminalis)- networks of enlarged capillaries surrounding the hypothalamic regulatory centres. Destruction of these organs reduces the ability of pyrogens to produce fever. Most studies in animals have failed to show, however, that pyrogenic cytokines pass from the circulation into the brain itself. Thus, it appears that both exogenous pyrogens and pyrogenic cytokines interact with the endothelium of these capillaries and that this interaction is the first in initiating fever- i.e., in raising the set point to febrile levels.
The key events in the production of fever are illustrated below figure:
7
\
Myeloid and endothelial cells are the primary cell types that produce pyrogenic cytokines. Pyrogenic cytokines such as IL-1,IL-6 and TNF are released from these cells and enter the systemic circulation. Although these circulating cytokines lead to fever by inducing the synthesis of PGE2, they also induce PGE2 in peripheral tissues. The increase in PGE2 in the periphery accounts for the nonspecific myalgia and arthralgias that often accompany fever. It is thought that some systemic PGE2 escapes destruction by the lung and gains access to the hypothalamus via the internal carotid. However, it is the elevation of PGE2 in the brain that starts the process of raising the hypothalamic set point for core temperature.
There are four receptors for PGE2, and each signals the cell in different ways. Of the four receptors, the third (EP3) is essential for fever: when the gene for this receptor is deleted in mice, no fever follows the injection of IL-1 or endotoxin. Deletion of other PGE2 receptor genes leaves the fever
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mechanism intact. Although PGE2 is essential for fever, it is not a neurotransmitter. Rather, the release of PGE2 from the brain side of the hypothalamic endothelium triggers the PGE2 receptor on glial cells, and this stimulation results in the t rapid release of cyclic adenosine 5’ monophosphate (cAMP), which is a neurotransmitter. The release of cAMP from the glial cells activates neuronal endings from the thermoregulatory center that extend into the area. The elevation of cAMP is thought to account for changes in the hypothalamic set point either directly or indirectly ( by inducing the release of neurotransmitters). Distinct receptors for microbial products are located on the hypothalamic endothelium. These receptors are called Toll-like receptors and are similar in many ways to IL-1 receptors. IL-1 receptors and Toll-like receptors share the same signal- transducing mechanism. Thus, the direct activation of Toll-like receptors or IL-1 receptors results in PGE2 production and fever.
Production of cytokines in the CNS
Cytokines produced in the brain may account for the hyperpyrexia of CNS haemorrhage, trauma, or infection. Viral infections of the CNS induce microglial and possibly neuronal production of IL-1, TNF, and IL-6. In experimental animals, the concentration of the cytokine required to cause fever is several orders of magnitude lower with direct injection into the brain substance or brain ventricles than with systemic injection. Therefore, cytokines produced in the CNS can raise the hypothalamic set point, bypassing the
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circumventricular organs. CNS cytokines likely account for the hyperpyrexia of CNS haemorrhage, trauma, or infection.
PYROGENS:
Pyrogens are of two types : 1). Exogenous pyrogens :
That originate outside the body (e.g., microbes, toxins, or other products of microbial origin).
2). Endogenous pyrogens :
Those derived from host cells (e.g., are host cell–derived (pyrogenic) cytokines that are the principal central mediators of the febrile response.(2).) FEBRILE PATTERN:
Continuous fever:
In this type of fever the patient have elevated temperature above normal and remains for a period of time without touching the baseline and the fluctuation does not exceed 0.6c in 24 hours, e.g. Typhoid, urinary tract infection, lobar pneumonia , typhus , or brucellosis. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
Continuous fever
10 Intermittent fever:
In this type of fever the patients have elevated temperature for a period of time but it touch the baseline in between. In septic or hectic type of intermittent fever, the diurnal variation elevation is extremely large, as occurs in septicaemia. Quotidian fever is a hectic fever occurring daily. e.g. malaria, kala-azar, or septicemia. Following are itstypes
Fever that occurs with periodicity of 24 hours is called Quotidian fever, typical of Malaria Fever that occurs on the first and third day is called Tertian fever, e.g P. Ovale and vivax, falciparum. Fever that occurs on first and fourth day is called Quartan fever. e.gPlasmodium malariae
11 Intermittent fever pattern
Remittent fever:
In this type of fever the patients have elevated temperatureand the fluctuation exceeds 0.60c, but it does not touch the baseline e.g., infective endocarditis.
Remittent fever pattern
Relapsing fever pattern:
In this type of fever the patients will have period of fever episode then followed by normal temperature for several days then again they have fever, e.gborrelia infection, rat bite fever.
12 Borrelia(relapsingpattern)
Pel-Ebstein fever: In this type of febrile pattern, the fever lasting for 3 to 10 days followed by an afebrile period of 3 to 10 days e.ghodgkinslymphomas
SADDLE BACK (BIPHASIC FEVER):
Patient have fever for several days followed by a period of reduced fever about one day then have additional several days of fever. These kind of fever episodes seen in dengue, rift valley fever, yellow fever, Colorado tick fever and viral fever like influenza.
13 Malaria fever chart
14 Thrombocytopenia: (3)
Thrombocytopenia may be defined as a subnormal number of platelets in the circulating blood. It is the most common cause of abnormal bleeding.
Despite the number and diversity of disorders that may be associated etiologically, thrombocytopenia results from only four processes:
1) Artifactual thrombocytopenia 2) Deficient platelet production 3) Accelerated platelet destruction
4) Abnormal distribution or pooling of the platelets within the body Pathophysiological classification of thrombocytopenia:
1)Artifactual thrombocytopenia :
Platelet clumping caused by anticoagulant-dependent immunoglobulin
Platelet satellitism
Giant platelets
2) Decreased platelet production:
Hypoplasia of megakaryocytes
Ineffective thrombopoiesis
Disorders of thrombopoietic control
Hereditary thrombocytopenias
15 3) Increased platelet destruction:
Caused by immunologic processes Autoimmune:
Idiopathic
Secondary: infections,pregnancy,collagen vascular disorders, lymphoproliferative disorders, drugs, miscellaneous
Alloimmune :
Neonatal thrombocytopenia
Post transfusion purpura
Caused by nonimmunologic processes
Thrombotic microangiopathies
i. Disseminated intravascular coagulation ii. Thrombotic thrombocytopenic purpura iii. Hemolytic-uremic syndrome
Platelet damage by abnormal vascular surfaces
Miscellaneous
i. Infection
ii. Massive blood transfusion
16 4) Abnormal platelet distribution or pooling
Disorders of the spleen (neoplastic, congestive, infiltrative, infectious,of unknown cause)
Hypothermia
Dilution of platelets with massive transfusions 5)Drug induced thrombocytopenia
Signs and symptoms in thrombocytopenias:
Signs :
Petechiaes
Purpuras ( dry , wet purpuras)
Ecchymosis
Rashes
Spleenomegaly SYMPTOMS :
Bleeding manifestations
Minor bleeding: Gum bleeding , mucosal bleeding, excessive menstrual bleed.
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Major bleeding : upper gastrointestinal bleed, lower gastrointestinal bleed, intracerebral bleeding, intraabdominal bleeding, retroperitoneal bleeding, retinal bleeding rarely it cause retroorbital bleeding.
Since there are many mechanisms for the development of thrombocytopenia in various diseases here we going to discuss about the most common infectious diseases and systemic illness that cause thrombocytopenia in tropical countries.
Mechanism of thrombocytopenia in Malaria
Thrombocytopenia is common to all the four human malarias and is caused by increased splenic clearance(4). Thrombocytopenia is associated with high levels of IL-10 and appropriately raised concentrations of thrombopoeitin (a key growth factor for platelet production)(5). Plasma concentrations of macrophage colony stimulating factor are high, which stimulate macrophage activity, and may increase platelet destruction(6). Platelet turnover is increased.
The role of platelet-bound antibody in malarial thrombocytopenia is controversial(7,8,9).
Erythrocytes containing mature parasites may activate the coagulation cascade directly (10).,and cytokine release is also procoagulant. The high plasma levels of P-selectin found in severe malaria may derive from platelets, (11)but could also come from vascular endothelium, as plasma concentrations of other
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endothelial derived proteins ( thrombomodulin, E-selectin, ICAM-1, VCAM-1) are elevated as well(12,13).
Coagulation cascade activity is directly proportional to disease severity,
(14).But hypofibrinogenaemia resulting from DIC is significant in less than 5%
of patients with severe malaria,and lethal haemorrhage is very unusual (15,16). DIC may lead to thrombocytopenia.
There is accelerated coagulation cascade activity with accelerated fibrinogen turnover, consumption of antithrombin III, reduced factor XIII,and increased concentrations of fibrin degradation productions in acute malaria. In severe infections, the prothrombin and partial thromboplastin times may be prolonged, and in occasional patients (<5%) bleeding may be significant. The coagulation cascade is activated via the intrinsic pathway.
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THROMBOCYTOPENIA IN DENGUE
Pathophysiology in Dengue fever:
The pathophysiological hallmarks of Dengue hemorrhagic fever are plasma leakage and abnormal haemostasis.
Following the bite of a Dengue virus (DENV) -infected mosquito, there is local viral replication in Langherhan’s cells and cutaneous dendritic cells, and spread to regional lymph nodes. Thereafter, the virus rapidly disseminates throughout the reticuloendothelial system and skin leading to viremia. The primary target cells for viral replication appear to be those of myeloid lineage- dendritic cells, macrophages and monocytes. The incubation period between the mosquito bite and onset of symptoms varies from 3-10 days. Viremia generally lasts for 4-5 days and the disappearance of virus from the blood correlated with the resolution of fever (17,18).
The most severe, and sometimes fatal, form of dengue is dengue hemorrhagic fever. The distinguishing pathophysiologic characteristic of dengue hemorrhagic fever is a transient and rapid increase in vascular permeability, thrombopathy with impaired platelet function and moderate to severe thrombocytopenia and coagulopathy, acute-type disseminated intravascular clotting is documented in severe cases, often with prolonged shock and responsible for severe bleeding.
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The plasma leakage syndrome is most often characterized by hemoconcentration and transudate accumulation across serosal surfaces (i.e, pleural effusions and ascites). In its extreme form ( dengue shock syndrome), hypovolemic shock ensues(19,20). The plasma leakage syndrome that distinguishes dengue hemorrhagic fever/dengue shock syndrome develops rapidly at the time of defervescence and clearance of viremia, and is transient(hours to days).
Primary infection with a DENV serotype produces long-term protective immunity against re-infection with the homologus serotype, but only short-time protective immunity against heterologous serotypes(21,22).The relative risk of developing dengue hemorrhagic fever/denge shock syndrome is increased 15 to 100 fold with sequential heterologous DENV infections compared with a primary DENV infection (23,24,25). The prevailing hypothesis to explain the apparent immunopathogenesis of dengue hemorrhagic fever has been antibody dependent enhancement of DENV infection (26,27,28).
The classical dengue fever begins with abrupt onset of fever, retro- orbital headache, backache,and severe myalgias (“breakbone fever”) (29,30,31). The febrile illness typically lasts for 5-7 days and can be accompanied by anorexia, nausea/vomiting and prolonged asthenia. There is accompanying leukopenia, thrombocytopenia and often mild hepatic transaminase elevation.
Petechiae may develop spontaneously, but most commonly, can be elicited in a positive tourniquet test(>10 or 20 petechiae/square inch on the forearm after
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inflation of a blood pressure cuff) (32). Clinically significant bleeding (e.g., epitaxis, gastrointestinal hemorrhage, menorrhagia/metrorrhagia) is much less common, but can occasionally be severe or life-threatening. Towards the end of the febrile period, the classic rash of dengue may appear ( Herman’s rash). It is a confluent erythematous macular rash over the extremities with scattered, well circumscribed areas of sparing( “ a sea of red with islands of normal skin”).
The appearance of this rash is essentially pathognomonic for a DENV infection.
Dengue hemorrhagic fever is the dengue clinical syndrome whose distinguishing feature is abrupt plasma leakage from the intravascular to the extravascular space. When severe, the decrease in plasma volume leads to hypotension and shock ( dengue shock syndrome ). Most often the hemorrhagic manifestations may only be a positive tourniquet test, or spontaneous skin or mucosal petechiae. Severe coagulopathy is nearly always seen in the context of profound shock and in multi-organ failure. The majority of serious morbidity and mortality caused by DENV infections is caused by a vascular leakage syndrome leading to hypotension and shock. Clinically significant hemorrhage can sometimes occur in the absence of vascular leakage syndrome, particularly in adults. Uncommon , but serious complications of DENV infections have been recognized and include hepatic necrosis, encephalopathy or encephalitis, and chorioretinitis(33,34).
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Dengue hemorrhagic fever case definition and severity classification:
Signs and symptoms of dengue fever and:
1. thrombocytopenia (platelet count<100000/cu.mm) and
2. evidence of plasma leakage (hematocrit rise more than 20% from baseline, pleural effusion, or ascites), and
3. hemorrhagic manifestation (see below)
DHF Grade I = criteria 1+2+ positive tourniquet test
DHF grade II = criteria 1+2+ spontaneous bleeding
DHF grade III = DHF grade I/II criteria+circulatory failure ( hypotension, weak pulse)
DHF grade IV = DHF grade I/II criteria + profound shock Case definition for “severe dengue”
Probable or laboratory-confirmed dengue and;
1. Severe plasma leakage(shock or fluid accumulation with respiratory distress), or
2. Severe hemorrhage ( as evaluated by clinician),or 3. Severe organ impairment:
Liver: AST or ALT more than 1000 U/ml
Central nervous system : impaired consciousness
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Heart and other organs Warning signs for severe dengue:
Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation
Mucosal bleed
Lethargy, restlessness
Liver enlargement >2 cm
Increase in hematocrit concurrent with rapid decrease in platelet count.
Treatment :
The treatment is mainly of supportive management, assess the patient general condition, hydration status and bleeding tendencies and platelets counts and treat accordingly.
Fluid management is very important in the treatment of dengue especially in case of dengue shock syndrome and dengue hemorrhagic fever.
0.9 % Normal saline and ringer lactate are the preferred choice of fluids in the management of dengue.
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Patients presenting with bleeding manifestation are supported with blood products transfusion. Dengue with co infection with other bacterial infections are promptly diagnosed and treat with appropriate antibiotics.
If patients with profound shock which is not recovered by i.v fluids and/or if it associated with sepsis, inotropes can be used in these conditions.
Prevention : The eradication of virus transmitting mosquito and clearance of the clean water sources, which is place for viral replication is the main stay of prevention of dengue.
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THROMBOCYTOPENIA IN LEPTOSPIROSIS
Leptospirosis is a zoonosis with protean manifestations. The commonly identified complications of acute renal failure and jaundice have been widely described and reviewed in a considerable number of literatures. Severe cases of leptospirosis often presents not only with renal failure and jaundice, but also with other organ involvement including myocarditis, aseptic meningitis, and hemorrhagic diathesis.
The hemorrhagic manifestations of leptospirosis occur in many ways.
Pulmonary hemorrhage is a dreaded complication because it is associated with a high mortality rate. In 1984, an epidemic of pulmonary hemorrhagic fever occurred in Korea. Extensive investigations were undertaken to determine the cause, including clinical, pathological and epidemiological studies of all possible causative agents. The investigations finally came up with leptospirosis as the culprit.
In the year 1995, an outbreak of an acute febrile illness and pulmonary hemorrhage occurred during the period of October to November. More than 2000 persons were affected and at least 40 patients died from acute pulmonary hemorrhage and respiratory insufficiency. The initial considerations were dengue hemorrhagic fever and the hantavirus pulmonary syndrome, but serologic tests detected anti-leptospiral antibodies and immunohistochemical
26
staining of tissues from fatal cases demonstrated leptospiral antigens present in various organs.
Together with myocarditis, pulmonary hemorrhage and GI bleeding were identified as common complications leading to death.
Thrombocytopenia in leptospirosis has received little attention. Most studies on the pathogenesis of leptospirosis focused on renal failure and jaundice.
With the outbreaks of pulmonary hemorrhage in association with leptospirosis, our focus should shift to the mechanisms causing the bleeding diathesis in this particular disease. Thrombocytopenia is thought to be fleeting, mild and rare.
However, reviews reported increasing prevalence of thrombocytopenia.
Some authors postulated that this could possibly be attributed todisseminated intravascular coagulation (DIC) or a toxin or cytotoxin mediated mechanism;
as a direct complication of leptospiral vasculitis as a general phenomenon of septicemia, or due to an undetected platelet antibody.
Whether either of these mechanisms is operating alone or in combination is uncertain and merits extensive investigation.
27
It is important for clinicians to be aware and to recognize the various ways in which leptospirosis can present. Although classically occurring as an acute febrile illness with renal failure and jaundice, the other less common manifestations may predominate. The changing pattern of the virulence of the disease could have been better explained by identifying the serovars involved.
It has been speculated that a new strain of leptospires may be responsible for the more severe presentation in some patients. Our poor yield in culture studies for Leptospira, and the unavailability of specific antigens for the different serovars makes this difficult.
Thrombocytopenia can occur in mild to moderate to severe forms;
majority of the platelet counts were between 20,000 and 80,000.Thrombocytopenia in leptospirosis was also associated with increased number of fatal complications. The presence of thrombocytopenia indicated a more severe form of leptospirosis.. Mortality rate was higher in the thrombocytopenic group compared to the non thrombocytopenic group.
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THROMBOCYTOPENIA IN TYPHOID FEVER
The haematological changes in typhoid fever are anemia, leucopoenia, eosinophilia, thrombocytopenia and sub clinical disseminated intravascular coagulation. Thrombocytopenia is one of the common finding amongst patients presenting with typhoid fever. The disease causes reversible bone marrow suppression. These haematological changes in typhoid diseases are mainly due to bone marrow suppression and hemophagocytosis.(35)
Many cases of typhoid fever have peripheral blood cytopenias that were not concurrent bone marrow suppression, suggesting a peripheral mechanism responsible for the blood dyscrasia in those cases(36). However, in other studies the patients suffering from typhoid fever with pancytopenia, bone marrow examination revealed extensive haemophagocytosis which possibly contributed to the pancytopenia. The term haemophagocytosis describes the pathological finding of activated macrophages and engulfing erythrocytes, leucocytes, platelets, and their precursors cell.
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THROMBOCYTOPENIA IN SEPSIS
Thrombocytopenia is one of the most common finding in critical illness and is commonly used in clinical trials of severe sepsis as a marker of hematologic organ dysfunction.
Nearly 30-40 % of patients in the ICU having platelets<1,00,000/mm3 . In a study of ICU patients sepsis was one of the major risk factor for thrombocytopenia.
Mechanism:
Sepsis induced thrombocytopenia is multifactorial in origin.
In experimental models of sepsis platelets adhere to activated endothelium in multiple organs. Following adhesion the activated platelets may either dislodge and return to the circulation or release their granule contents and undergo irreversible aggregation with vicious metamorphosis.
Inflammatory mediators and bacterial products such as endotoxins can contribute to sepsis induced thrombocytopenia by enhancing platelet reactivity and adhesivity.
Phagocytosis of platelets by reticuloendothelial elements may also contribute to cytopenias in sepsis.
30
Thrombocytopenia in sepsis may be due to mechanism of immune complex mediated destruction of platelets.
Nonspecific platelet-associated antibodies can be detected in up to 30%
of ICU patients. In these patients, non-pathogenic IgG presumably binds to bacterial products on the surface of platelets, to an altered platelet surface, or as immune complexes. A subset of patients with platelet-associated antibodies have autoantibodies directed against glycoprotein IIb/IIIa. These antibodies have been implicated in the pathogenesis of immune thrombocytopenic purpura and, although not proved, may play a role in mediating sepsis-induced thrombocytopenia.
Microscopy of bone marrow in patients with sepsis often demonstrated hemophagocytichistiocytes. In a prospective study of 50 patients with sepsis hemophagocytosis was identified in 32 patients (64%). This process appears to be a function of elevated levels of macrophage colony stimulated factors and is correlated with the presence and extent of multiorgan dysfunction. In some patients with sepsis antibodies to specific antiplatelet antigens such as GPIIb/IIIa and GP Ib/IX have been detected.
The acute phase response is often characterized by increased platelet counts (thrombocytosis). However, patients who are admitted to the ICU with or without underlying sepsis are more commonly diagnosed as thrombocytopenia. Thrombocytopenia occurs in up to 20% of medical ICU and
31
35% of surgical ICU admissions(37,38,39). Sepsis is a clear risk factor for thrombocytopenia, with an estimated incidence of 35% to 59%(40,41). In addition, there is an inverse relationship between the severity of sepsis and the platelet count.
In a prospective study of critically ill patients with thrombocytopenia only 34% had a diagnosis of DIC. Secondary consumptive thrombocytopenia and DIC are most common in case of sepsis. In addition to sepsis-related mechanisms, other causes of thrombocytopenia should be considered in the critically ill patient. For example, thrombocytopenia may occur as a complication of heparin therapy. Other types of drug induced thrombocytopenia are rare in the ICU setting. Dilutional thrombocytopenia may occur in patients with trauma or those who have undergone complicated surgery. Preexisting underlying disease, including cancer and immune thrombocytopenic purpura, may also contribute to a low platelet count. Given the inverse correlation between platelet count and mortality and the proposed association of platelet activation with tissue injury and organ dysfunction, the development of thrombocytopenia in the patient with sepsis is best regarded as maladaptive.
32 Clinical Manifestations and Diagnosis
Thrombocytopenia is a common cause of bleeding in the ICU setting.
Patients with thrombocytopenia may have petechiae, purpura, bruising, or bleeding. Thrombocytopenia is diagnosed on the basis of the complete blood cell count. A peripheral smear may show evidence of platelet clumping. If that is the case, the platelet count should be remeasured in blood withdrawn into a non-EDTA containing tube. If the thrombocytopenia is associated with consumptive coagulopathy, the DIC screen may be abnormal, and the peripheral smear may show schistocytes. Although patients with sepsis may have increased platelet- associated IgG, testing for this gives nonspecific results and does not help to guide therapy.
Prognosis
Thrombocytopenia is a predictor of mortality in patients in the ICU and in patients with severe sepsis(42). The degree and duration of thrombocytopenia, as well as the net change in the platelet count, are important determinants of survival(43,44,45). Interestingly, once the platelet count decreases lower than 100 x109/L, mortality continues to increase, whereas the risk of bleeding does not increase.
33 Treatment
Patients with severe thrombocytopenia should be treated with platelet transfusions. Although guidelines for prophylactic transfusions in patients with chemotherapy-induced thrombocytopenia have been established, the threshold for transfusions for the thrombocytopenic patient with sepsis is not as clear. In the absence of confounding factors, patients should probably receive transfusions when the platelet count is less than 10000 – 150000/cu.mm. If the patient has concomitant coagulopathy (eg. liver disease), active bleeding, or platelet dysfunction (eg, uremia), the transfusion threshold should be increased.
34
MATERIALS AND METHODS
Materials
The study was done in patients admitted in medical ward and IMCU of Coimbatore Medical college and hospital , Coimbatore over a period of one year. All the test done with due permission from the Institutional Ethical Committee and informed consent from the subjects.
Inclusion criteria:
1) Patients with age group more 18 years of age,
2) Patients admitted with complaints of fever and having thrombocytopenia in complete hemogram with platelet count of less than 150000/cu.mm.
Exclusion criteria:
1) Patients taking drugs that causes thrombocytopenia (immunosupressants/ chemotherapy /antiplatelets)
2) Pregnant cases.
3) Patients previously having chronic thrombocytopenic conditions due to other cause were excluded.
4) Patients who are not given consent.
35 PERIOD OF STUDY:
All the patients in the study group were age more than 18 years admitted as in patients between July 2017 to June 2018 in Medicine department in Coimbatore Medical college Hospital for fever were evaluated.
DESIGN OF STUDY: prospective study
Methods
All patients admitted in Coimbatore medical college and hospital with fever and thrombocytopenia were evaluated. Detailed history was taken in all patients admitted over study period regarding duration of fever , occupation and travel history. History of bleeding manifestation and other symptoms were noted.
Vitals signs like pulse rate , respiratory rate, blood pressure, temperature, oxygen saturation were noted. Signs regarding central nervous system, respiratory system, renal ,haemotological and hepatic involvement were noted.
Investigations like complete hemogram , urine routine , renal function test, liver function test , PT,APTT,INR , Chest X ray , USG abdomen were done on admission.
36
At the time of admission with the clinical examination, laboratory investigation values, systemic involvement and the outcome of patients scoring system was derived .
Evaluation
Patients admitted with fever in our hospital during the study period were taken complete hemogram and those patients having thrombocytopenia of platelet count less than 150000 cells/cm.mm were followed up and evaluated clinically and basic investigations were analysed. Detailed history were taken in all the patients in study group and their vitals signs like pulse rate, respiratory rate, temperature , blood pressure ,oxygen saturation were noted.
Infectious diseases work up like ESR, urine analysis, IgM dengue, IgM leptospirosis, MSAT, peripheral smear, blood culture and sensitivity, urine culture and sensitivity, Widal test were taken.
A detailed clinical examination of the patients in our study group were done.
The signs and symptoms of various systemic involvement were analysed clinically by following methods :
Central nervous system involvement is analysed by history of altered sensorium, seizures, impaired level of consciousness with signs of meningeal irritation like neck stiffness etc..
37
Respiratory system involvement is evaluated by history of breathing difficulty, cough, sputum production with signs of tachypenea, fall in oxygen saturation and infiltrates in chest x ray.
Patients presenting with heamotological manifestions like bleeding tendencies, with signs of petechiae, purpura, ecchymosis or bleeding from any orifices were noted.
Renal system involvement is evaluated by history of decreased urine output, hematuria and by elevation of urea and creatinine.
Hepatic involvement is analyzed by history of jaundice, features of volume overload and by elevation in liver enzymes and abnormal coagulation profile.
Those patients who are treated with platelet transfusions were noted.
Those patients who were died and cause for the death were noted.
38
RESULTS
In our study, 100 patients presenting with fever and thrombocytopenia at Coimbatore medical college and hospital were randomly selected in the study period who met the inclusion criteria as said earlier.
In those 100 cases of study population, after critical analysis of patients clinical conditions, vitals , systemic involvement and their outcome regarding mortality of the patients, a scoring system was derived.
39
AGE DISTRIBUTION
In the analysis of 100 cases of febrile thrombocytopenia , most of the patients age group was below 30 years of age. The age factor is statistically insignificant for cause of mortality
Table 1 : AGE DISTRIBUTION
AGE IN YEARS NO OF PATIENTS PERCENTAGE
<30 54 54%
31-40 30 30%
> 40 16 16%
Chart 1 : AGE DISTRIBUTION
<30 31-40 54%
30%
> 40 16%
AGE DISTRIBUTION
40
Table 2 : AGE VS OUTCOME
OUTCOME
AGE IN YEARS
MEAN SD
DEAD 28.61 6.53
ALIVE 31.05 8.13
UNPAIRED T TEST P VALUE - 0.304 NON SIGNIFICANT
Chart 2 : AGE VS OUTCOME
28.61 31.05
D E A D A L I V E
MEAN AGE VS OUTCOME
41
SEX DISTRIBUTION
In the analysis of 100 cases of febrile thrombocytopenia , the number of males were 55 and females were 45 . The sex factor is statistically insignificant for cause of mortality
Table 3 : SEX DISTRIBUTION
SEX NO OF PATIENTS PERCENTAGE
MALE 55 55%
FEMALE 45 45%
Chart 3 : SEX DISTRIBUTION
55%
45%
SEX DISTRIBUTION
MALE FEMALE
42
Table 4 :SEX VS OUTCOME
SEX
OUTCOME
DEAD ALIVE
MALE 7 48
FEMALE 6 39
CHI SQUARE TEST P VALUE - 0.929 NON SIGNIFICANT
Chart 4 : SEX VS OUTCOME
7 48
6 39
D E A D A L I V E
O U T C O M E
SEX VS OUTCOME
MALE FEMALE
43
PULSE RATE
The pulse rate for all the cases were recorded at the time of admission and found to be patients having increased pulse rate has high chance of mortality.
Table 5 : PULSE RATE
PULSE RATE NO OF PATIENTS PERCENTAGE
MORE THAN 100 37 37%
LESS THAN 100 63 63%
Chart 5 : PULSE RATE
37%
63%
PULSE RATE
MORE THAN 100 LESS THAN 100
44
Table 6 : PULSE RATE VS OUTCOME
OUTCOME
PULSE RATE
MEAN SD
DEAD 106.3 9.59
ALIVE 95.04 13.7
UNPAIRED T TEST P VALUE - 0.005
SIGNIFICANT
Chart 6 : PULSE RATE VS OUTCOME
106.3 95.04
D E A D A L I V E
OUTCOME VS PULSE RATE
45
SYSTOLIC BLOOD PRESSURE
In our study of 100 cases of febrile thrombocytopenia, systolic blood pressure doesn’t have statistically significant value for mortality.
Table 7 : SYSTOLIC BLOOD PRESSURE
SYSTOLIC BP NO OF PATIENTS PERCENTAGE
< 100mmHg 25 25%
> 100mmHg 75 75%
Chart 7 : SYSTOLIC BLOOD PRESSURE
25%
75%
SYSTOLIC BP
< 100mmHg
> 100mmHg
46
Table 8 : SYSTOLIC BLOOD PRESSURE VS OUTCOME
OUTCOME
SYSTOLIC BP
MEAN SD
DEAD 99.23 14.97
ALIVE 107.72 16.64
UNPAIRED T TEST P VALUE - 0.086 INSIGNIFICANT
Chart 8 : SYSTOLIC BLOOD PRESSURE VS OUTCOME
99.23 107.72
D E A D A L I V E
OUTCOME VS SYSTOLIC BP
47
TEMPRATURE
Most the patients have higher level of temperature more than 100 deg F and the temperature alone is statistically insignificant in view of mortality.
Table 9 : TEMPERATURE
TEMPERATURE NO OF PATIENTS PERCENTAGE
HIGH 93 93%
NORMAL 7 7%
Chart 9 : TEMPERATURE
93%
7%
TEMPERATURE
HIGH NORMAL
48
Table 10 : TEMPERATURE VS OUTCOME
OUTCOME
TEMPERATURE
MEAN SD
DEAD 100.46 1.76
ALIVE 99.78 10.5
UNPAIRED T TEST P VALUE - 0.052 INSIGNIFICANT
Chart 10 : TEMPERATURE VS OUTCOME
100.46
99.78
99.4 99.6 99.8 100 100.2 100.4 100.6
DEAD ALIVE
MEAN TEMP VS OUTCOME
49
OXYGEN SATURATION
Patients having lower oxygen saturation at the time of admission has worse prognosis.
Table 11 :OXYGEN SATURATION
SPO2 NO OF PATIENTS PERCENTAGE
< 96% 3 3%
> 96% 97 97%
Chart 11 : OXYGEN SATURATION
3%
97%
SPO2
< 96%
> 96%
50
Table 12 : OXYGEN SATURATION VS OUTCOME
OUTCOME
SPO2 %
MEAN SD
DEAD 96.38 3.7
ALIVE 97.96 7.45
UNPAIRED T TEST P VALUE - 0.003
SIGNIFICANT
Chart 12 : OXYGEN SATURATION VS OUTCOME
95.5 96 96.5 97 97.5 98
DEAD ALIVE
96.38
97.96
MEAN SPO2 VS OUTCOME
51
RESPIRATORY RATE
Among 100 cases , 63 patients admitted with increased respiratory rate ,but it doesn’t have significant relation to mortality.
Table 13 : RESPIRATORY RATE
RESPIRATORY RATE NO OF PATIENTS PERCENTAGE
MORE THAN 16 63 63%
LESS THAN 16 37 37%
Chart 13 : RESPIRATORY RATE
MORE THAN 16 63%
LESS THAN 16 37%
RESPIRATORY RATE
52
Table 14 : RESPIRATORY RATE VS OUTCOME
OUTCOME
RESPIRATORY RATE
MEAN SD
DEAD 19 4.63
ALIVE 17.75 2.56
UNPAIRED T TEST P VALUE - 0.153 NON SIGNIFICANT
Chart 14 : RESPIRATORY RATE VS OUTCOME
19 17.75
D E A D A L I V E
MEAN RR VS OUTCOME
53
HAEMATOCRIT
Among the 100 cases, 58 patients have normal , 3 have increased and 39 have decreased heamatocrit values. Patients with increased haematocrit had worse prognosis.
Table 15 : HAEMATOCRIT
HAEMATOCRIT NO OF PATIENTS PERCENTAGE
INCREASED 3 3%
NORMAL 58 58%
DECREASED 39 39%
Chart 15 : HAEMATOCRIT
3%
58%
39%
HAEMATOCRIT
INCREASED NORMAL DECREASED
54
Table 16: HAEMATOCRIT VS OUTCOME
OUTCOME
HAEMATOCRIT
MEAN SD
DEAD 45 4.81
ALIVE 41.96 3.93
UNPAIRED T TEST P VALUE - 0.013
SIGNIFICANT
Chart 16: HAEMATOCRIT VS OUTCOME
45 41.96
D E A D A L I V E
MEAN HAEMATOCRIT VS OUTCOME
55
PLATELET COUNT
Among the 100 cases , 44 patients have platelet count less than 40000 cells/cu.mm, 41 patients have platelet count between 40001-80000 cells/cu.mm, 15 patients have platelet count more than 80000 cells/cu.mm.
Table 17 : PLATELET COUNT PLATELET COUNT
Cells/cu.mm
NO OF PATIENTS PERCENTAGE
< 40000 44 44%
40001-80000 41 41%
> 80000 15 15%
Chart 17 : PLATELET COUNT
< 40000 44%
40001-80000 41%
> 80000 15%
PLATELET COUNT
56
Table 18 : PLATELET COUNT VS OUTCOME
OUTCOME
PLATELET COUNT
MEAN SD
DEAD 22769 20228
ALIVE 51919 30314
UNPAIRED T TEST P VALUE - 0.001
SIGNIFICANT
Chart 18 : PLATELET COUNT VS OUTCOME
22769
51919
0 10000 20000 30000 40000 50000 60000
DEAD ALIVE
MEAN PLATELET COUNT VS OUTCOME
57
CNS INVOLVEMENT
Among the 100 cases, 6 patients had central nervous system complications like altered sensorium, seizures and encephalitis. Among the total death in our study, 2 patients have central nervous system involvement.
Table 19 : CNS INVOLVEMENT
CNS INVOLVEMENT NO OF PATIENTS PERCENTAGE
PRESENT 6 6%
ABSENT 94 94%
Chart 19 : CNS INVOLVEMENT
6%
94%
CNS INVOLVEMENT
PRESENT ABSENT
58
Table 20 : CNS INVOLVEMENT VS OUTCOME
OUTCOME
CNS INVOLVEMENT
PRESENT ABSENT
DEAD 2 11
ALIVE 4 83
CHI SQUARE TEST P VALUE - 0.127 NON SIGNIFICANT
Chart 20 : CNS INVOLVEMENT VS OUTCOME
2 4
11
83
0 10 20 30 40 50 60 70 80 90
DEAD ALIVE
CNS INVOLVEMENT VS OUTCOME
CNS INVOLVEMENT CNS INVOLVEMENT
59
RESPIRATORY SYSTEM INVOLVEMENT
Out of 100 cases of febrile thrombocytopenia , only 6 patients have respiratory involvement which doesn’t have any significance in the outcome of patients.
Table 21 : RESPIRATORY SYSTEM INVOLVEMENT
RS INVOLVEMENT NO OF PATIENTS PERCENTAGE
PRESENT 6 6%
ABSENT 94 94%
Chart 21 : RESPIRATORY SYSTEM INVOLVEMENT
6%
94%
RS INVOLVEMENT
PRESENT ABSENT
60
Table 22 :RS INVOLVEMENT VS OUTCOME
OUTCOME
RS INVOLVEMENT
PRESENT ABSENT
DEAD 2 11
ALIVE 4 83
CHI SQUARE TEST P VALUE - 0.127 NON SIGNIFICANT
Chart 22 : RS INVOLVEMENT VS OUTCOME
2 4
11
83
0 10 20 30 40 50 60 70 80 90
DEAD ALIVE
RS INVOLVEMENT VS OUTCOME
RS INVOLVEMENT RS INVOLVEMENT
61
HAEMATOLOGICAL INVOLVEMENT
Out of 100 cases , only 3 patients have haematological involvement which doesn’t have any significance in the outcome of patients.
Table 23 : HAEMATOLOGICAL INVOLVEMENT HAEMOTOLOGICAL
INVOLVEMENT
NO OF
PATIENTS PERCENTAGE
PRESENT 3 3%
ABSENT 97 97%
Chart 23 : HAEMATOLOGICAL INVOLVEMENT
PRESENT 3%
ABSENT 97%
HAEMOTOLOGICAL INVOLVEMENT
62
Table 24 : HAEMATOLOGICAL INVOLVEMENT VS OUTCOME
OUTCOME
HAEMOTOLOGICAL INCOLVEMENT
PRESENT ABSENT
DEAD 1 12
ALIVE 2 85
CHI SQUARE TEST P VALUE - 0.288 NON SIGNIFICANT
Chart 24 : HAEMATOLOGICAL INVOLVEMENT VS OUTCOME
1
12 2
85
0 10 20 30 40 50 60 70 80 90
PRESENT ABSENT
HAEMOTOLOGICAL INCOLVEMENT
HAEMOTOLOGICAL INVOLVEMENT
DEAD ALIVE
63
RENAL INVOLVEMENT
Out of 100 cases , 13 patients have renal involvement .Patients admitted with febrile thrombocytopenia having renal involvement have worse prognosis.
Table 25 : RENAL INVOLVEMENT
RENAL INVOLVEMENT NO OF PATIENTS PERCENTAGE
PRESENT 13 13%
ABSENT 87 87%
Chart 25 : RENAL INVOLVEMENT
13%
87%
RENAL INVOLVEMENT
PRESENT ABSENT
64
Table 26 : RENAL INVOLVEMENT VS OUTCOME
OUTCOME
RENAL INVOLVEMENT
PRESENT ABSENT
DEAD 5 8
ALIVE 8 79
CHI SQUARE TEST P VALUE - 0.003
SIGNIFICANT
Chart 26 : RENAL INVOLVEMENT VS OUTCOME
5 88 79
D E A D A L I V E
RENAL INVOLVEMENT VS OUTCOME
RENAL INVOLVEMENT RENAL INVOLVEMENT
65
HEPATIC INVOLVEMENT
Out of 100 cases , 14 patients have hepatic involvement .Patients admitted with febrile thrombocytopenia having hepatic involvement have worse prognosis.
Table 27 : HEPATIC INVOLVEMENT
HEPATIC INVOLVEMENT NO OF PATIENTS PERCENTAGE
PRESENT 14 14%
ABSENT 86 86%
Chart 27 : HEPATIC INVOLVEMENT
14%
86%
HEPATIC INVOLVEMENT
PRESENT ABSENT
66
Table 28 : HEPATIC INVOLVEMENT VS OUTCOME
OUTCOME
HEPATIC INVOLVEMENT
PRESENT ABSENT
DEAD 7 6
ALIVE 7 80
CHI SQUARE TEST P VALUE - 0.001
SIGNIFICANT
Chart 28 : HEPATIC INVOLVEMENT VS OUTCOME
7 76 80
D E A D A L I V E
HEPATIC INVOLVEMENT
HEPATIC INVOLVEMENT HEPATIC INVOLVEMENT
67 BLEEDING
Among the 100 cases, 31 patients presented with bleeding manifestations. Among the total death in our study , 8 of them have bleeding manifestations at time of admission.
Table 29 : BLEEDING MANIFESTATIONS
BLEEDING NO OF PATIENTS PERCENTAGE
PRESENT 31 31%
ABSENT 69 69%
Chart 29 : BLEEDING MANIFESTATIONS
31%
69%
BLEEDING
PRESENT ABSENT
68
Table 30 : BLEEDING MANIFESTATIONS VS OUTCOME
OUTCOME
BLEEDING
PRESENT ABSENT
DEAD 8 5
ALIVE 23 64
CHI SQUARE TEST P VALUE - 0.011
SIGNIFICANT
Chart 30 : BLEEDING MANIFESTATIONS VS OUTCOME
8
23
5
64
0 10 20 30 40 50 60 70
DEAD ALIVE
BLEEDING
BLEEDING BLEEDING
69
PLATELET TRANSFUSION
In our study of 100 cases of febrile thrombocytopenia, platelet transfusion was given for 40 patients.
Table 31 : PLATELET TRANSFUSION
PLATELET TRANSFUSION NO OF PATIENTS PERCENTAGE
YES 40 40%
NO 60 60%
Chart 31 : PLATELET TRANSFUSION
40%
60%
PLATELET TRANSFUSION
YES NO
