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Vol 2 | Issue 4 | Oct – Dec 2023                                                                          Indian J Pharm Drug Studies | 183  

Original Article 

Incidence of thrombocytopenia one month after initiation of heparin 

during hemodialysis: An observational study 

Krisnendu Das1, Utpal Bhui2, Arghya Majumdar3, Sanmoy Karmakar4 

From, 1Assistant Professor, School of Pharmaceutical Sciences, The Neotia University, Diamond Harbour, West Bengal, 2PG 

Student, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 

Punjab, 3Director & Head of Nephrology, Department of Medicine, AMRI Hospitals, 4Professor, Department of 

Pharmacology, Jadavpur University, Kolkata, West Bengal, India 

ABSTRACT 

Thrombocytopenia, a platelet count below 150 × 109/L, may be acquired or congenital. In patients with chronic kidney disease 

on hemodialysis, thrombocytopenia may be multi-factorial. However, the most worrisome of these is heparin-induced 

thrombocytopenia (HIT), as it causes thrombosis in various vital organs in addition to bleeding. Heparin is the mainstay of 

anticoagulation on hemodialysis to prevent clotting in the extra-corporeal circuit. HIT may be either Type 1 (non-immune) or 

Type 2 (immune). The protocol of testing for the presence of thrombocytopenia 1 month after starting heparin on hemodialysis 

is seldom followed and the exact incidence of HIT in eastern India is unknown. We studied hemodialysis patients in a tertiary 

care hospital in Kolkata over a period of 9 months. All of them had platelet counts checked after starting hemodialysis as per 

protocol. No patients had symptoms or signs of HIT. A drop in platelet count was noticed in 3 patients, but it was transient and 

attributable to other causes. It did not necessitate stopping of heparin and the platelet count spontaneously improved.   So, it is 

reassuring that HIT is rare in the eastern part of India. 

Key words: Contaminated heparin, Oversulfated chondroitin sulphate, Heparin-induced thrombocytopenia, End-stage renal 

disease, Anti heparin platelet factor 4 antibodies 

hrombocytopenia, or low platelet count, defined as 

a platelet count below 150 × 109/L, can be broadly 

classified as congenital and acquired. Acquired 

thrombocytopenia could be immune or non-immune [1]. 

Thrombocytopenia could be a result of decreased marrow 

production, increased destruction or sequestration/ 

consumption in the periphery, or a combination of 

decreased production and sequestration. Initial steps in the 

evaluation of thrombocytopenia include a review of the 

peripheral blood smear to exclude pseudo-

thrombocytopenia due to platelet clumping [2].  

The peripheral blood smear may also provide clues 

toward other causes of thrombocytopenia when combined 

with the complete blood count and a good patient history  

Access this article online 

Received – 06th August 2023 

Initial Review – 16th August 2023 

Accepted – 22nd August 2023  

Quick Response Code 

and physical examination. Platelet size and the presence of 

schistocytes, polychromasia, or spherocytes are some of 

the other features on the peripheral blood smear that help 

in diagnosing the etiology of thrombocytopenia [3]. 

Thrombocytopenia could be a serious medical 

condition such as thrombotic thrombocytopenic purpura 

(TTP) or heparin-induced thrombocytopenia (HIT). 

Therefore, it is always important for the treating physician 

to evaluate thrombocytopenia in a timely fashion so that 

the treatment for some of the serious conditions is not 

delayed [4]. The relevance of thrombocytopenia in the 

individual patient is variable and depends on the clinical 

presentation. Because platelets play an essential role in 

preserving vessel wall integrity [5].  

Thrombocytopenia is associated with a defect of 

primary hemostasis. Clinically significant spontaneous  

_______________________________________ 

Correspondence to: Krishnenedu Das, 36A, Mahanirban 

Road, Kolkata - 700029, West Bengal, India. Email: 

krishnendas96@gmail.com Tel.: +91 9874377408 

T 

mailto:krishnendas96@gmail.com


Das K et al.                                             Heparin- Initiated Thrombocytopenia: Hemodialysis’s 1-Month Study 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                          Indian J Pharm Drug Studies | 184  

bleeding does not usually occur until the platelet count is 

less than 10-20 109/L [6]. However, the presence of 

thrombocytopenia can aggravate surgical or traumatic 

bleeding or prevent the administration of effective 

treatment for several conditions (eg, antiviral therapy for 

chronic hepatitis C virus infection or cancer 

chemotherapy) [7].  

In other situations, a low platelet count is the only 

initial manifestation of an underlying disorder that poses 

greater risks than thrombocytopenia itself (eg, HIV 

infection or myelodysplastic syndromes) or is an important 

marker of disease activity (eg, thrombotic microang-

iopathies) [8]. Establishing the cause of thrombocytopenia 

has obvious clinical repercussions, but is sometimes quite 

challenging. This is particularly the case for hospitalized 

patients, in whom thrombocytopenia appears frequently in 

the background of a multisystem disorder and may be 

determined by multiple mechanisms [9].  

Conversely, in the outpatient setting, thrombocytopenia 

is often isolated and asymptomatic, and the diagnosis of 

the specific cause is usually straightforward. 

Thrombocytopenia in pregnancy deserves special 

consideration because of the possible consequences on the 

fetus [10]. A structured approach to the diagnosis of 

thrombocytopenia involves the integration of clinical 

findings and appropriate support from the laboratory and 

other medical disciplines [11]. 

MATERIAL AND METHODS 

The study was conducted in a prospective mode and was 

based on patients who were observed during the study 

period from 21st September 2020 to 4th May 2021. The 

study was carried out in the dialysis department of AMRI 

Group of Hospitals, Kolkata, Dhakuria. Formal permission 

for the study has been obtained from the respective IEC.  

RESULT 

Statistical analysis shows that in comparison of platelet 

count according to age and sex before and after heparin, 

61-70 age group patients have more changes in platelet 

count than other age groups. Females have more changes 

in platelet count than males. No patients had symptoms or 

signs of HIT. Two patients dropped platelet count below 

1L and one patient below 1.5L but did not.  Develop 

thrombotic events. So heparin was continued. The 

thrombocytopenia was attributed to transient episodes of 

sepsis. The platelet count spontaneously improved again to 

>1L of two patients and one patient’s platelet count 

improved again to >1.5L (Table 1). 

Table 1 – Patient details 

Age Sex Platelet count before 

heparin 

Platelet count after 

heparin  

58 F 2.8      2.2 

73 M 1.7      1.5 

70 M 3.68        2 

69 M 1.7      1.5 

70 F 1.7      1.5 

59 F 1.5     1.51 

66 M 1.5      1.6 

78 M 1.5      1.6 

65 M 1.1     0.75 

65 M 1.6      1.6 

68 M 1.6      0.9 

58 M 1.5      1.3 

53 M 1.6      1.6 

55 M 2.1      2.2 

83 F 2.2       2 

64 F 3.68       2 

56 M 3       2 

66 M 1.9     1.6 

51 M 2.27     2.2 

The pie chart (Figure 1) illustrates the platelet count 

before and after heparin according to age, whereas it 

reveals that the high platelet count before and after heparin 

is bigger at 61 to 70 age compared to other age groups. 

According to Figure 2, which shows the platelet count 

before and after heparin according to sex, male patients 

have higher platelet counts both before and after heparin 

than female patients. 

Figure 3 shows based on age and sex, it compares platelet 

counts before and after heparin, with the rate of platelet 

counts before heparin being higher than the rate of platelet 

counts after heparin. This shows that once heparin was 

started during hemodialysis, the amount of platelet count 

decreased.  

Figure 4 shows the differences in platelet count before and 

after heparin based on age, clearly demonstrating that the 

platelet count before heparin is higher than the platelet 

count after heparin at various age groups. The changes in 

platelet count are also significant, with a 0.56 change from 

61 to 70 years old.  

The graph charts (Figure 5) illustrate how the platelet 

count has changed according to sex, with the platelet count 

before heparin being higher than the platelet count 

following heparin. Additionally, compared to men, women 

have greater variations in platelet count, which is 0.53.  



Das K et al.                                             Heparin- Initiated Thrombocytopenia: Hemodialysis’s 1-Month Study 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                          Indian J Pharm Drug Studies | 185  

 
Figure 1 – Platelet count before and after heparin at 

different age groups. 

 
Figure 2 -Platelet count before and after initiation of 

heparin at different sex groups. 

 
Figure 3 - Drop of platelet count before and after heparin based on age and sex. 

 
Figure 4 – Changes in platelet count before and after heparin based on age. 

 

Figure 5 - Changes in platelet count before and after heparin based on sex. 

36.8

47.4

10.5
5.3

AGE

51-60 61-70 71-80 81-90

26.3

73.7

SEX

FEMALE MALE

2.03

1.66

0.00

0.50

1.00

1.50

2.00

2.50

 BEFORE HEPARIN AFTER HEPARIN

PLATELET COUNT

0.00

0.50

1.00

1.50

2.00

2.50

51-60 61-70 71-80 81-90

2.11 2.05

1.60

2.20

1.86

1.49 1.55

2.00

0.25

0.56

0.05
0.20

PLATELET COUNT & AGE  

PLATELET COUNT BEFORE HEPARIN PLATELET COUNT AFTER HEPARIN CHANGE IN PLATELET COUNT

0.00

1.00

2.00

3.00

FEMALE MALE

2.38
1.911.84

1.60

0.53 0.31

PLATELET COUNT & SEX

PLATELET COUNT BEFORE HEPARIN PLATELET COUNT AFTER HEPARIN CHANGE IN PLATELET COUNT



Das K et al.                                             Heparin- Initiated Thrombocytopenia: Hemodialysis’s 1-Month Study 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                          Indian J Pharm Drug Studies | 186  

DISCUSSION 

Takfumi Matsuo et al. conducted a study on Heparin 

Induced Thrombocytopenia and Haemodialysis in dialysis 

patients with an unexpected fall in the platelet count, 

and/or unexplained thrombotic events, particularly visible 

clotting in the circuit under an adequate heparin dose, that 

begins between 5 and 10 days ( between 7 and 30 days, 

mostly by the third to fifth session) after heparin initiation 

ELISA test result came positive, so in this case Alternative 

non-heparin anticoagulants like a direct thrombin inhibitor 

Argatroban was used as an alternative to heparin. 

Argatroban contributed to the rapid recovery of the platelet 

count and the disappearance of visible circuit clotting [12]. 

Robert E.Cronin et al., is conducted a study on 

Unfractionated Heparin for Haemodialysisin the 10,564 

maintenance hemodialysis patients in the United Kingdom, 

the prevalence of HIT was 0.26per 100 patients and only 

17% of these had complications related to the disorder.  

The disorder was typically discovered 5–10 days following 

exposure to unfractionated heparin and was characterized 

by a drop in platelet count and variable occurrence of a 

clotting event.  Arterial disorders.  The drop in platelet 

count was typically 30–50% below baseline and rarely 

reduced to the low levels seen with other drug-induced 

thrombocytopenias. When heparin was withdrawn, platelet 

counts typically recover to baseline within 2 weeks [13]. 

Jenny I. Shen, MD, MS and Wolfgang C. Winkelmayer 

et al. conducted a study on the Use and Safety of 

Unfractionated Heparin for Anticoagulation during 

Maintenance Hemodialysis in a 50-year-old man with a 

history of diabetes mellitus and end-stage renal disease 

(ESRD) became hypotensive 15 minutes into his dialysis 

session. He had been receiving maintenance hemodialysis 

through a left arteriovenous fistula 3 times a week for the 

past 5years without complication. He does not have a 

history of a bleeding disorder but takes 81 mg of aspirin 

daily.  However, his abdominal pain worsened, so the 

hemodialysis treatment was discontinued and he was sent 

to the emergency department for further evaluation, later 

he had been transfused a total of 8 units of packed red 

blood cells. His hemoglobin level had stabilized at 9.5 

g/dL. His platelet levels never decreased. The patient 

underwent anticoagulant-free hemodialysis acutely. After 

discharge, he was instructed to avoid taking aspirin [14]. 

C. WU et al., is conducted a study on  Rivaroxaban for 

the treatment of suspected or confirmed heparin-induced 

thrombocytopenia studying Twenty-two consecutive 

adults with suspected or confirmed HIT received 

rivaroxaban 15 mg bid until a local HIT assay result was 

available. Participants with a positive local assay result 

continued rivaroxaban 15 mg bid until platelet recovery 

(or until day 21 if they had acute thrombosis at study 

entry), then stepped down to rivaroxaban 20 mg daily until 

day 30. The primary outcome measure, incidence of new 

symptomatic, objectively-confirmed venous and arterial 

thromboembolism at 30 days, occurred in one HIT-

positive participant (4.5%; 95% confidence interval) and 

one HIT-positive participant required limb amputation 

despite platelet recovery. Platelet recovery was achieved in 

nine out of 10 HIT-positive patients with 

thrombocytopenia [15]. 

Timothy K. Liem, MD et al., conducted a study on 

Lepirudin as a safe and effective anticoagulant for patients 

with heparin-associated antiplatelet antibodiesinEighteen 

HAAb-positive patients received lepirudin. Lepirudin use 

was analyzed for indication, duration, and effectiveness of 

anticoagulation, and adverse events. HAAb presence was 

determined by platelet aggregation .9 had previous 

documentation of HAAb, 6 had thrombocytopenia while 

receiving heparin, and 3 had HAAb after a thrombotic 

event. The indications for lepirudin anticoagulation 

included thromboembolism prophylaxis arterial 

thrombosis pulmonary embolus or deep venous thrombosis 

and one each for atrial fibrillation, myocardial infarction, 

artificial heart valves, and hemodialysis access. The 

average duration of therapy was 4.04 days. Fifteen patients 

achieved adequate anticoagulation (activated partial 

thromboplastin time [aPTT] ratio > 2.0) with lepirudin. 

Seven patients had aPTTs that were sometimes supra 

therapeutic (aPTT> 100 seconds) but did not bleed. In all 

patients who had heparin-induced thrombocytopenia, 

platelet counts were normalized while they received 

lepirudin. There were two complications: one patient fell 

and had a calf hematoma (aPTT ratio 3.24) [16]. 

Joana Gameiro et al. conducted a study on  

Haemodialysis-related-heparin-induced thrombocytopenia 

Case series and Literature review in 5 patients between the 

ages 71 to 85 and had a history of hypertension, had 

chronic kidney disease, between this patient some had 

multiple myeloma and some had a bacterial infection, 

atrial fibrilization, and anemia. These 5 patients came with 

thrombocytopenia with low levels of platelet count in the 

hospital, warfarin and sodium citrate gave good results in 

platelet recovery and thrombocytopenia [17]. 

Makoto Harada et al. conducted a study on A Case of 

Heparin-Induced Thrombocytopenia That Developed in 

the Therapeutic Course of Anti-Neutrophil Cytoplasmic 

Antibody-Associated Vasculitis in an 87-year-old woman 

who presented with appetite loss and leg edema was 



Das K et al.                                             Heparin- Initiated Thrombocytopenia: Hemodialysis’s 1-Month Study 

Vol 2 | Issue 4 | Oct – Dec 2023                                                                          Indian J Pharm Drug Studies | 187  

admitted for evaluation. Blood examination revealed an 

inflammatory response (C-reactive protein level was 7.85 

mg/dL), kidney dysfunction (blood urea nitrogen was 37.4 

mg/dL, and the serum creatinine level was 2.25 mg/dL), 

and hypoalbuminemia. Heparin calcium therapy was also 

administered. Reduction of 50% or more of the platelet 

count and a platelet decrease between 5 and 10 days after 

using heparin are consistent. Additionally, because the 

FDP-D-dimer was high, she might have had thrombosis. 

Heparin was discontinued 29 days after hospitalization, 

and argatroban therapy was administered. After starting 

argatroban therapy, her platelet count gradually increased. 

Fifty-two days after her hospitalization, the platelet count 

improved to 200,000/μL.  However, because kidney 

function was not recovered, she was administered 

maintenance hemodialysis [18]. 

In this study, 19 patients experienced HIT after taking 

heparin recently (within 14 days). Through the analysis of 

sociodemographic data, it was found that the percentage of 

male patients (73.7%) was higher than the percentage of 

female patients (26.3%) (Figure 2). Male preponderance is 

seen in gender distribution in our study, which is similar to 

reports from other studies in countries of Asia. In India, 

less number of females may be due to higher illiteracy, 

social stigma, and the need for the male relative to be 

concerned and accompany the female for hospital visits. 

Maximum patients in this study were of age group 61-70 

years (47.4 %) followed by 51-60years (36.8 %), 71-80 years 

(10.5 %), and 81- 90 years (5.3%) (Figure 1). A bimodal 

distribution is seen with the incidence of HIT. With a peak 

incidence in elderly patients and then in the first decade.  

HIT has been recorded in individuals receiving 

hemodialysis while utilizing heparin anticoagulation, 

though heparin exposure for other purposes could not be 

ruled out. This study revealed 19 patients who experienced 

HIT after taking heparin recently (within 14 days) just to 

keep their blood vessels healthy while receiving renal 

replacement therapy. None of the patients showed an 

abrupt (within hours) development of HIT after heparin 

exposure, indicating a longer period possibly up to four 

months without prior heparin exposure. The immediate 

discontinuation of heparin and the initiation of alternative 

anticoagulation are recommended for treating patients with 

HIT. This approach decreases the 38–76% risk of 

thrombosis that persists for days to weeks (Figure 3). 

Platelet counts typically recover more rapidly when 

patients receive alternative anticoagulant therapy, 

compared with historical control therapy. In the patients 

reported here, partial recovery of platelet counts occurred 

before argatroban discontinuation, the rate of new 

thrombosis was similar to that reported in previous studies 

of argatroban therapy in HIT, no one died of 

thromboembolic complications, and the bleeding risk was 

acceptably low (Figure 4, 5).  

CONCLUSION  

In 9-month research conducted in a Kolkata tertiary care 

hemodialysis facility, no incidences of HIT were found. A 

small number of patients developed thrombocytopenia 

without developing thrombotic events. So heparin kept 

going. The platelet counts spontaneously improved. As a 

result, we can conclude that HIT is probably fairly 

uncommon in the eastern part of India and the direct 

thrombin inhibitors lepirudin and bivalirudin, which are 

primarily cleared by renal and renal/enzymatic processes, 

respectively, have also been used for HIT therapy. 

However, argatroban, which is metabolized by the liver, is 

generally considered to be a better choice for patients with 

renal failure. The present findings emphasize the 

importance of heightened awareness of HIT in heparin-

treated patients undergoing hemodialysis and of suspecting. 

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How to cite this article: Krisnendu Das, Utpal Bhui, 

Arghya Majumdar, Sanmoy Karmakar. Incidence of 

thrombocytopenia one month after initiation of heparin 

during hemodialysis: An observational study. Indian J 

Pharm Drug Studies. 2023; 2(4):183-188. 

Funding: None            Conflict of Interest: None Stated 

 


