Background: In tropical countries like India, thrombocytopenia is commonly encountered by clinicians in any speciality. Thrombocytopenia present as asymptomatic condition to sometimes becomes a life-threatening condition requiring blood transfusion in various etiological conditions. Infections like malaria and dengue are invariably associated to thrombocytopenia with changing trends in clinical features. Infection is the commonest cause of thrombocytopenia. The objective of study was to evaluate the different causes of thrombocytopenia along with study of clinical profile and laboratory parameters in patients with thrombocytopenia. Methods: A cross-sectional hospital based study was conducted in Department of Medicine at Tertiary Care Hospital from April 2019 to October 2019. This study comprises cases of thrombocytopenia of age more than 14 years admitted with platelet count <1 lack/mm3, whereas patients with already diagnosed with causes associated with thrombocytopenia such as malignancy and chemotherapy induced thrombocytopenia, idiopathic thrombocytopenic purpura, cirrhosis of liver were excluded. Results: Study shows almost 46.6 % of total patients were below age of 30 years and 53.4% patients were above 30 years of age. The highest incidence of thrombocytopenia was seen in the age group of 21-30 years (26.6%), followed by 31-40 (25.8%) and 12-20 years (20%). The most common diseases that causes thrombocytopenia were infections (65.80%) [i.e. Dengue (31.67%), Malaria (25.0%), Enteric fever (3.33%), HIV (0.8%), and DIC (5.0%)]. Megaloblastic anaemia (18.33%) were common in younger population. Conclusion: Study concluded that most common causes of thrombocytopenia were infections (65.8%) and megaloblastic anemia (18.33%). Bleeding manifestations were present in 28.33% of patients and the most common site of bleeding was skin and mucous membrane. The main etiological cause of bleeding in this study was dengue hemorrhagic fever followed by malaria and megaloblastic anaemia
Nature has designed a complex but ingenious system to maintain blood in the vascular system fluid and free from clots, yet allow the rapid formation of solid plug to close ruptures as other forms of injury to blood vessels. This process is referred to as normal hemostasis. It has long been thought that the primary role of the platelet in circulation is to help maintain primary hemostasis and blood flow within the vessel1,2. Thrombocytopenia is one of the most common hematologic disorders, characterized by an abnormally low number of platelets from multiple causes. The normal count of thrombocytes (platelets) is between 1,50,000 and 4,50,000 per microliter. Thrombocytopenia is defined as a platelet count below the 150 × 109/L, the 2.5th lower percentile of the normal platelet count distribution3. Platelet counts higher than 150 × 109/L do not lead to clinical problems unless platelet dysfunction coexists with the low count; rather, they are picked up on a routine complete blood count. Medical help is usually sought by a patient with platelet counts less than 30 × 109/L, suffering from spontaneous bruising and purpura or with continuous/relatively long-lasting bleeding from injuries and wounds. Clinically significant spontaneous bleeding does not usually occur until the platelet count is less than 10 × 109/L. In disease state, decreased platelet production is due either to a decrease in the megakaryocyte mass (virtually always a decrease in production) or to a failure of delivery of an appropriate number of viable platelets by an adequate megakaryocyte cytoplasmic mass, a process termed ‘ineffective platelet production’4. Direct destruction of megakaryocytes, their progenitors or both can be observed after administration of chemotherapeutic agents or irradiation5. Thrombocytopenia is the most common hematologic abnormality in severe alcoholism6. Alcohol abuse may result in thrombocytopenia due to several mechanisms, including ineffective production related to folate deficiency (which may lead to severe thrombocytopenia) and increased splenic pooling due to portal hypertension (which usually results in a modest decline in platelets). A mild shortening of platelet survival has been reported. However, ethanol itself can be directly toxic to the marrow 7,8. Mild thrombocytopenia is frequently associated with viral infection9. Although the pathophysiologic mechanisms have not been systematically sought, a production deficit is probably important in the etiology of many of the cases. Megakaryocytes containing inclusion bodies are seen in varicella, cytomegalovirus, infectious mononucleosis, chickenpox, dengue and other hemorrhagic fevers, hepatitis and parvovirus infections 10,11,12. Live measles virus vaccination can also induce thrombocytopenia due to decreased production13. This study aims to determine the relative frequency of different disease conditions presenting as newly found thrombocytopenia in adult patients and the proportion of patients who had bleeding manifestations. This study also aims to study the different bleeding manifestations in order of their commonness of occurring and the percentage of patients requiring interventions like platelet substitutes, steroids, splenectomy and also to determine whether a low platelet count or presence of bleeding manifestation was considered more often as indicator for platelet transfusions.
This cross-sectional hospital-based study was conducted amongst 120 patients in Department of General Medicine at Tertiary Care Hospital from period of April 2019 To October 2019 over the period of 7 months.
Method of collection of Data:
Inclusion criteria
Exclusion criteria
* If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear is evaluated and a platelet count determined in blood collected into sodium citrate (blue top tube) or heparin (green top tube) to avoid pseudo thrombocytopenia cases.
Sample size
Those patients fulfill the inclusion and exclusion criteria and randomly selected 120 patients were enrolled for the study. Detailed clinical history was noted in each patient including site of bleeding, past history of drug and major medical illness in the past. Detailed physical examination was carried out in all patients. Routine Investigation in the form of peripheral smear, complete blood count, malaria antigen test, ultrasonography abdomen, chest x-ray, Renal function test, Liver function test, Coagulation profile etc. were done in all patients. The special investigations like Bone marrow examination, Serum widal, serology for leptospirosis, Dengue serology, Coomb’s test, Serum Vitamin B12 level, G6PD Test, LE Cells, Sucrose Lysis Test, RA Factor, ANA/Anti-Ds DNA, NCCT brain etc. were done as and when required. All the patients were treated with disease specific treatment and platelet transfusion was given as per indication. If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear is evaluated and a platelet count determined in blood collected into sodium citrate (blue top tube) or heparin (green top tube) to avoid pseudo thrombocytopenia cases.
All patients included in the study were followed up during their course in the hospital. The trend of their platelet counts was recorded. The decision as to when the platelet counts were repeated was that of the treating physician. The bleeding manifestations patients presented with or developed during their course in hospital were recorded. The diagnosis made in each of these cases was noted down. The proportion of study patients requiring interventions to improve platelet count like platelet transfusion, steroids and the reason for such intervention was recorded. Proportion of patients receiving platelet transfusions because of presence of a bleeding manifestation and proportion requiring prophylactic platelet transfusion were determined.
During the study period of 7 months (April 2019 to October 2019), 120 patients satisfied the inclusion criteria were included in the study. There were 68 males (mean age: 39.7 years) and 52 females (mean age: 35.4 years) in the study population. Largest age group in current study is between 21-40 years (52.4 %).
Table 1: Age Wise Distribution of Study Population
AGE GROUP (YEARS) |
|
|
NO OF PATIENTS |
(%) |
|
14-20 |
24 |
20 |
21-30 |
32 |
26.6 |
31-40 |
31 |
25.8 |
41-50 |
22 |
18.3 |
51-60 |
6 |
5 |
>60 |
5 |
4.2 |
TOTAL |
120 |
100 |
Table 2: Sex Wise Distribution of Study Population
SEX |
NO. OF PATIENTS |
(%) |
MALE |
68 |
57 |
FEMALE |
52 |
43 |
TOTAL |
120 |
100 |
Infectious conditions were most common cause of thrombocytopenia in this study. Common infections causing thrombocytopenia are dengue; malaria; bacterial infections causing sepsis and DIC; enteric fever. The commonest etiology responsible for newly diagnosed thrombocytopenia in adult patients admitted was found to be dengue/dengue like fever. 38 patients were diagnosed to have dengue/dengue like fever making up 31.67% of the total number of cases. Malaria was a close second with 30 cases (25%). The patients with malaria plasmodium falciparum were the cause for thrombocytopenia in 12 patients (40%) followed by plasmodium vivax with 18 patients (60%).
TABLE 3: ETIOLOGY
ETIOLOGY OF THROMBOCYTOPENIA |
|
|
NO. OF PATIENTS |
(%) |
|
DENGUE / DENGUE LIKE FEVER |
38 |
31.66 |
MALARIA |
30 |
25 |
MEGALOBLASTIC ANAEMIA |
22 |
18.33 |
ENTERIC FEVER |
4 |
3.33 |
CIRRHOSIS OF LEVER |
14 |
11.67 |
HELLP SYNDROME |
1 |
0.8 |
DIC |
6 |
5 |
ITP |
2 |
1.6 |
HIV |
1 |
0.8 |
OTHERS/UNKWOWN |
2 |
1.6 |
TOTAL |
120 |
100 |
Out of 120 patients included in study 34 patients had bleeding manifestations as compared to comparison study in which 32 (32%) had bleeding manifestation; some of the patients manifested bleeding at two or more site. Other site of bleeding included bleeding from intra venous lines that was seen in 2 patients.
Table 4: Hemorrhagic Manifestations Associated with Thrombocytopenia
SITE OF BLEEDING |
|
|
NO OF PATIENTS(n=120*) |
(%) |
|
SKIN AND MUCOUS MEMBRANE (PATECHIAE, ECCHYMOSIS, PURPURA) |
17 |
50 |
GUM BLEEDING |
8 |
23.5 |
EPISTAXIS |
5 |
14.7 |
HEMATEMESIS |
2 |
6.25 |
MALENA |
6 |
17.61 |
BLEEDING PER RECTUM |
1 |
2.94 |
INTRACRANIAL HEMMORHAGE |
1 |
2.94 |
BLEEDING PER VAGINA |
3 |
8.82 |
HEMATURIA |
1 |
2.94 |
SUBCONJUCTIVAL HEMORRHAGE |
1 |
2.94 |
OTHERS |
2 |
6.25 |
*Some of the patients had more than one bleeding manifestation.
Bleeding manifestations secondary to thrombocytopenia were seen most commonly with Platelet Count < 10,000/μL(18 patients) and 16 patients with platelet count 10,000-20,000/μL. There were 11 patients in the 20,000-50,000/μL group had bleeding. The occurrence of bleeding was least in the 50,000-1,00,000/L group with 2 cases of bleeding.
Table 5: Correlation Of Bleeding Site with Platelet Count
SITE OF BLEEDING |
PLETELETCOUNT <10,000 |
PLETELETCOUNT 10,000-20,000 |
PLETELETCOUNT 20,000->50,000 |
PLETELETCOUNT 50,000 |
SKIN AND MUCOUS MEMBRANE |
6 |
5 |
5 |
1 |
GUM BLEEDING |
5 |
2 |
1 |
0 |
HEMATEMESIS |
0 |
0 |
1 |
1 |
MALENA |
3 |
2 |
1 |
0 |
BLEEDING PER RECTUM |
0 |
1 |
0 |
0 |
BLEEDING PER VAGINA |
1 |
1 |
1 |
0 |
EPISTAXIS |
2 |
2 |
1 |
0 |
INTRACRANIAL HEMMORHAGE |
1 |
0 |
0 |
0 |
SUBCONJUCTIVAL HEMORRHAGE |
0 |
1 |
0 |
0 |
OTHERS |
0 |
2 |
1 |
0 |
TABLE 6: ORGANOMEGALY
ORGANOMEGALY |
NO. OF PATIENTS |
(%) |
SPLENOMEGALY |
32 |
26.6 |
HEPATOMEGALY |
7 |
5.8 |
HEPATOSPLENOMEGALY |
6 |
5 |
40 patients were given platelet transfusions (PRC), of which 12 had platelet count <10,000 and 28 patient had platelet count >10,000. Out of 12 patients with platelet count <10,000; 10 patient had bleeding manifestations; in 2 patients platelet transfusions was given prophylactically. One patient with ITP with Platelet counts below 10,000 presented with minor increase in per vaginal bleeding (menorrhagia); without significant fall in Hb; she was treated with iv steroids. Out of 28 patients given platelet transfusions with platelet count >10,000, 24 patient had bleeding manifestations; in 4 patient platelet transfusions was given prophylactically. Patients with platelet count >10,000 and who presented without significant bleeding were treated with disease specific therapy in form of iv steroids, antibiotics, vitamins, immune modulators and other form of therapy specific to cause.
Table 7: Treatment According To Platelets
PLETELET COUNT <10,000 |
PLETELET COUNT >10,000 |
||
TRANSFUSION |
DISEASE SPECIFIC TREATMENT |
TRANSFUSION |
DISEASE SPECIFIC TREATMENT |
12 |
1 |
28 |
68 |
A total number of 120 patients were included in the study during the study period of 6 months from April 2019 to October 2019. Similar study was done by Shah H. R., Vaghani B. D., Gohel P.2, Virani B. K. (Department of Medicine, GMERSMC, Ahmedabad, India, Department of Pathology, B J Medical College, Ahmedabad, India, Department of Medicine, B J Medical College, Ahmedabad, India).This study is taken as a reference study and comparison between various parameters was done ; Largest age group in current study is between 21-40 years (52.4 %); and in comparison study is between 21-40 years (52%).
Table 8: Age Wise Distribution Of Study Population
AGE GROUP (YEARS) |
CURRENT STUDY |
SHAH et al14 |
||
NO. OF PATIENTS |
(%) |
NO. OF PATIENTS |
(%) |
|
14-20 |
24 |
20 |
24 |
24 |
21-30 |
32 |
26.6 |
30 |
30 |
31-40 |
31 |
25.8 |
22 |
22 |
41-50 |
22 |
18.3 |
14 |
14 |
51-60 |
6 |
5 |
9 |
9 |
>60 |
5 |
4.2 |
1 |
6.25 |
TOTAL |
120 |
100 |
100 |
100 |
TABLE 9: ETIOLOGY
ETIOLOGY OF THROMBOCYTOPENIA |
CURRENT STUDY |
SHAH et al14 |
||
NO. OF PATIENTS |
(%) |
NO. OF PATIENTS |
(%) |
|
DENGUE / DENGUE LIKE FEVER |
38 |
31.66 |
18 |
18 |
MALARIA |
30 |
25 |
31 |
31 |
MEGALOBLASTIC ANEMIA |
22 |
18.33 |
26 |
26 |
ENTERIC FEVER |
4 |
3.33 |
5 |
5 |
CIRRHOSIS OF LEVER |
14 |
11.67 |
9 |
9 |
HELLP SYNDROME |
1 |
0.8 |
2 |
2 |
DIC |
6 |
5 |
2 |
2 |
ITP |
2 |
1.6 |
6 |
6 |
HIV |
1 |
0.8 |
1 |
1 |
OTHERS/UNKNOWN |
2 |
1.6 |
3 |
3 |
TOTAL |
120 |
100 |
100 |
100 |
Malaria (31%) was found most common cause of thrombocytopenia in comparison study while dengue (31.66) is leading cause of thrombocytopenia in current study. Megaloblastic anaemia is most common non infectious cause of thrombocytopenia in both studies. The commonest bleeding manifestation secondary to thrombocytopenia was skin and mucous membrane manifestation in form of PATECHIAE, ECCHYMOSIS PURPURA which was seen in 17 patients i.e 50% of total patients with bleeding and in 37.5% of patients with bleeding in comparison study.
Table 10: Site Of Bleeding
SITE OF BLEEDING |
CURRENT STUDY |
SHAH et al |
||
NO OF PATIENTS (n=120*) |
(%) |
NO. OF PATIENTS (n=100*) |
(%) |
|
SKIN AND MUCOUS MEMBRANE (PATECHIAE, ECCHYMOSIS, PURPURA) |
17 |
50 |
12 |
37.5 |
GUM BLEEDING |
8 |
23.5 |
9 |
28.5 |
EPISTAXIS |
5 |
14.7 |
2 |
6.25 |
HEMATEMESIS |
2 |
6.25 |
5 |
15.62 |
MALENA |
6 |
17.61 |
3 |
9.37 |
BLEEDING PER RECTUM |
1 |
2.94 |
2 |
6.25 |
INTRACRANIAL HEMMORHAGE |
1 |
2.94 |
1 |
3.12 |
BLEEDING PER VAGINA |
3 |
8.82 |
7 |
21.87 |
HEMATURIA |
1 |
2.94 |
4 |
12.5 |
SUBCONJUCTIVAL HEMORRHAGE |
1 |
2.94 |
1 |
3.12 |
OTHERS |
2 |
6.25 |
1 |
3.12 |
*Some of the patients had more than one bleeding manifestations.
Table 11: Comparison Of Organomegaly
ORGANOMEGALY |
CURRENT STUDY |
SHAH et al |
||
NO. OF PATIENTS |
(%) |
NO. OF PATIENTS |
(%) |
|
SPLENOMEGALY |
32 |
26.6 |
25 |
25 |
HEPATOMEGALY |
7 |
5.8 |
7 |
7 |
HEPATOSPLENOMEGALY |
6 |
5 |
6 |
6 |
Incidence of splenomegaly and hepatomegaly was found similar in both studies.
Table 12: Comparison Of Treatment of Thrombocytopenia
TRANSFUSION |
DISEASE SPECIFIC TREATMENT |
||
CURRENT STUDY |
SHAH et al |
CURRENT STUDY |
SHAH et al
|
36(30%) |
34 (34%) |
69(57.5%) |
76(76%) |
Platelet transfusion was required in 40 (33.3%) of patients in current study out of which 12 patients had platelet count <10,000 and 28 patients had Platelet count >10,000. in comparison study 34 patients required Platelet transfusion of which 11 patients had platelet counts <10,000 and 23 patients had Pleteletcount >10,000. Disease specific treatment was required in 69 (57.5%) of patients in current study out of which 01 patient had platelet count <10,000 and 68 patients had platelet count >10,0000. In comparison study, 76 patients required disease specific treatment out of which 11 patients had platelet counts >10,000.
This study shows that commonest age group of patients presenting with thrombocytopenia at a tertiary care centre is between 21-40 yrs (53%). There is no clear-cut sexual predilection for patients presenting with thrombocytopenia; however, number of male patients affected is slightly higher than female. Infectious conditions are most common cause in adult patients who are newly detected to have thrombocytopenia at admission to medicine with febrile illness. Dengue / dengue like illness remains commonest infection causing thrombocytopenia; followed by malaria; and bacterial infections causing sepsis. Therefore, the presence of thrombocytopenia raises suspicion of these diseases and emphasises the need for prompt treatment of the patients. Megaloblastic anemia is second most common cause (most common noninfectious cause). Early diagnosis of megaloblastic anaemia is crucial for achieving better treatment outcomes. Majority (One fourth) of patients with platelet count less than 1,00,000/μL tend to have bleeding manifestation. Bleeding manifestations were seen in 30% of the study population. 52.94% of these patients had platelet count < 10,000/μL. Commonest bleeding manifestation is that of skin and mucous membranes in form of patechiae, ecchymosis, purpura followed by gum bleeding and only one patient had ICH, which turned out fatal. In this study, 36 patients (30%) received blood transfusion out of that 12 patients had platelet count less than 10000/mm3 and 24 patients had platelet count more than 10000/mm3. To this day, questions remain unanswered about the specific threshold for transfusion of blood products appropriately. These thresholds vary according to the severity and complexity at the time of presentation. With timely diagnosis and appropriate treatment better clinical outcome can be achieved in most of cases.
LIMITATIONS OF THE STUDY
This is an institution-based study conducted in patients admitted in Department of Medicine at a tertiary care center and is not so much informative of the patterns of the disease involving in the community. Patients admitted in other departments were not included. The study population was minimal only hundred and twenty cases. Larger community-based studies are needed in future to find out the exact incidence and prevalence of patients having thrombocytopenia with different etiologies.
ABBREVIATIONS
EDTA – ETHYLENE DIAMINE TETRAACETIC ACID
G6PD – GLUCOSE-6-PHPSPHATASE DEFICIENCY
LE Cells – LUPUS ERYTHEMATOSUS Cells
RA Factor – RHEUMATOID Factor
ANA/Anti-Ds DNA – ANTINUCLEAR ANTIBODY/ Anti-DOUBLE STRANDED DEOXYREBONUCLEIC ACID
NCCT – NON-CONTRAST COMPUTED TOMOGRAPHY
DIC – DISSEMINATED INTRAVASCULAR COAGULATION
ITP – IDIOPATHIC THROMBOCYTOPENIC PURPURA
HIV – HUMAN IMMUNODEFICIENCY VIRUS
GI – GASTROINTESTINAL BLEED
ICH – INTRACRANIAL HAEMORRHAGE
PRC – PACKED RED CELL
FFP – FRESH FROZEN PLASMA
HELLP – HAEMOLYSIS, ELEVATED LIVER ENZYMES, LOW PLATELET COUNT