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 Table of Contents  
Year : 2021  |  Volume : 11  |  Issue : 5  |  Page : 245-247

Heparin-induced thrombocytopenia

Department of Critical Care Medicine, Sir Gangaram Hospital, Delhi, India

Date of Submission08-Oct-2020
Date of Decision16-Jun-2021
Date of Acceptance31-Aug-2021
Date of Web Publication30-Oct-2021

Correspondence Address:
Prakash Shastri
Department of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmrp.cmrp_77_21

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How to cite this article:
Shastri P, Kumar S. Heparin-induced thrombocytopenia. Curr Med Res Pract 2021;11:245-7

How to cite this URL:
Shastri P, Kumar S. Heparin-induced thrombocytopenia. Curr Med Res Pract [serial online] 2021 [cited 2022 Jan 17];11:245-7. Available from: http://www.cmrpjournal.org/text.asp?2021/11/5/245/329706

  Introduction Top

Heparin-induced thrombocytopenia (HIT) occurs in 5% to 10% of the patients receiving unfractionated heparin (UFH), typically within 4–15 days after starting treatment, but as early as 1 day in those who have prior heparin exposure.[1] The disorder may be associated with arterial and venous thromboembolic event-heparin-induced thrombocytopenia-thrombosis (HITT) where the mortality rate may go up to 30%. The incidence rate of HIT is 5.6% and HITT is 0.8% in Indians.[2]

  Case Report Top

A 64-year-old female was admitted on September 29, 2018, to the hospital with severe gastroenteritis and acute kidney injury. She was a known case of diabetes mellitus type-2, hypertension, chronic kidney disease (never dialysed) and hypothyroidism. Her routine investigations except for renal function tests were normal. HbA1C was 7.5 and procalcitonin levels were 2.4. Blood and urine cultures were sterile. She recovered after two sessions of haemodialysis done through a double lumen dialysis catheter in the right femoral vein.

She was discharged on October 3, after removal of her femoral catheter but was re-admitted on October 7, with weakness of right half of body and decreased level of consciousness. She had swelling of the right lower limb and bluish-black discoloration of the right toe. She was shifted to the intensive care unit (ICU) for further management.

On examination, she was obese, drowsy with a Glasgow Coma Scale of E3 V4 M4, pupils equal and reacting (both direct and consensual), right side hemiplegia but no facial weakness. Other organ systems were normal. She had swelling with erythema of the right lower limb extending up to the abdomen. Peripheral pulses were could not be palpated because of extensive swelling in right lower limb and cyanosis was noted over the tip of all toes. Investigations revealed Hb – 9.1 g/dl, TLC – 20,040/cu mm, platelets – 39,000/μL, BUN/creatinine – 55/1.5 mg/dl and Na/K – 141/4.4 mEq/L. Cultures sent from blood and urine were sterile and procalcitonin levels were 2.6. Blood sugar on admission was 264 mg/dl (HbA1C 8.6) and she was started on insulin. Non-contrast computer tomography of the head showed an infarct in the right middle cerebral artery territory.

Lower extremity duplex scan of right lower limb done showed occlusive thrombus in the right external iliac vein (EIV) extending to the popliteal vein. Arterial Doppler: right ATA 100 cm/s, triphasic flows, PTA 120 cm/sec triphasic flow. 2D echo showed concentric left ventricular hypertrophy, no regional wall motion abnormality, trace MR/TR, moderate pulmonary hypertension (PASP – 54 mmHg). Magnetic resonance imaging brain showed acute infarct involving left middle cerebral artery territory. As she had undergone dialysis 8 days back which also uses heparin to prevent blood clotting in extracorporeal circuits, HITT was high on suspicion besides other hypercoagulable states including antiphospholipid antibody syndrome. Vasculitis and thrombophilia screen was negative. D-dimer was 0.99 mcg/ml and pulmonary thromboembolism was ruled out by computed tomography (CT) pulmonary angiogram. CT Chest showed bilateral pleural effusion, irregular areas of consolidation and ground-glass opacity in both lung fields suggestive of fluid overload. Bone marrow aspiration reported adequate cellular bone marrow showing all haematopoietic elements with an increase in megakaryocytes suggesting peripheral destruction of platelets. No schistocytes were seen in the peripheral smear which ruled out intravascular haemolysis. Antiphospholipid antibodies such as B2 glycoprotein I (<3.0AU/ml) and anticardiolipin antibodies (ACA IgM – 5.9MPL U/ml) were negative. Antinuclear antibodies (c-ANCA and p-ANCA) and tests for hypercoagulability panel were negative.

The calculated HIT score was >6, so we did the rapid gel card test (DiaMed: Rapid-ID gel microtyping system BIO-RAD UK) which is a rapid assay for the detection of antiplatelet factor 4 (PF4)/heparin antibodies. The test was reported as positive and further heparin-induced platelet aggregation (HIPA Chrolog model 490-2D. agro/link version 5 software PA, USA) test was also positive. In view of the clinical profile, positive test reports of anti-HPF4 antibody and functional assay for HIT the picture were consistent with HITT.

She underwent venography and mechanical thrombectomy of right EIV, CIV, SFV, under local anaesthesia on October 15, 2018. Check venography was done on October 16, 2017, to rule out any residual thrombus in the distal veins. She was treated with fondaparinux. Her further clinical course was complicated due to pneumonia for which antibiotics and antifungals were given. She also needed NIV during this period and one session of heparin-free dialysis was done. She was discharged in stable condition 16 days after admission, and fondaparinux was replaced with new oral anticoagulant (factor X inhibitor) rivaroxaban.

  Discussion Top

HIT is the most common non-haemorrhagic complication of heparin. It is caused by antibodies-directed complexes containing heparin and an endogenous platelet protein, PF4.

Acute thrombocytopenia occurring immediately after heparin administration has been described in animals in 1942.[3] Type I HIT – it is a non-immune phenomenon and is generally short lived. The more serious immune-mediated complication type II HIT was first reported in 1948.[4] The clinical manifestation of the condition was first described in 1973 and includes concurrent manifestation of thrombocytopenia and thrombosis during heparin therapy. It may lead to life or limb-threatening ischaemia.[5]

Conventionally, 4T score[6],[7] is used for estimating pre-test probability of the disease. The 4Ts incorporates essential features of disease (timing of heparin therapy, complications of thrombocytopenia, thrombosis and exclusion of other causes) and categorises the risk based on the cumulative score (low risk: 0–3; intermediate risk: 4–5 and high risk: 6–8). Low scores (0–3) have very high negative predictive value (≈99%) to rule out the disease.

Confirmation of the diagnosis of HIT is made by laboratory evidence of anti-PF4/heparin antibodies, by platelet activation assays ('functional') or by immunoassays.[8]

Serotonin-release assay (SRA) is considered to be the gold standard for the diagnosis of HIT. However, this test requires a specialised laboratory for the radioactivity assay. Literature has found that the platelet aggregation test is comparable to the SRA.[8]

This patient developed thrombocytopenia after 8 days of heparin exposure (during dialysis) along with thrombosis. Her nadir platelet count was 30,000/μL, and there were no strong alternative causes for thrombocytopenia. Her 4T score was associated with high probability of HIT. Patients in ICU have other comorbid conditions that pre-dispose them to thrombocytopenia resulting from other causes, i.e., sepsis, disseminated intravascular coagulation, intravascular haemolysis (thrombotic microangiopathy TMA), pharmacologic agents, etc., and it may be difficult to be certain of the diagnosis of HIT. Therefore, laboratory confirmation of the diagnosis is often desirable understanding the limitation that no clinically available test is absolute, and clinical suspicion and judgement remain paramount.[9]

The patient at risk includes those with a thrombotic episode such as acute pulmonary thromboembolism (deep vein thrombosis-pulmonary embolism [DVT-PE], acute coronary syndromes, cerebrovascular accidents and limb ischaemia. Effective treatment options include withdrawing heparin and use of direct thrombin inhibitors (bivalirudin, argatroban and lepiridin). LMWH is less prone to produce HIT. Fondaparinux, a synthetic pentasaccharide LMWH, is being increasingly used off-label for the management of HIT. It does not crossreact with HIT antibodies and has not been implicated as a cause of HIT in case reports.[10] A few case series have reported on the safety and efficacy of new oral anticoagulants (NOAC). Rivaroxaban has been studied in a small cohort of 22 patients with HIT and was found to be safe without the occurrence of new thrombotic events.[11] However, presently, there is little evidence to recommend the routine use of NOAC in the management of HIT.

  Conclusion Top

UFH is widely used in cardiovascular surgeries and LMWH is often used in critically ill, bedridden patient for prophylaxis of DVT and PE.

HIT is common and potentially serious disorder in ICU.[10] It is a prothrombotic condition. Think about HIT in every ICU patient especially those with low platelets and try to elicit history of heparin exposure.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986;67:27-30.  Back to cited text no. 1
Kotwal J, Chaudhary S, Manoj MG, Hasnain S, Nair V, Luthra M. Heparin: Induced thrombocytopenia: Incidence and laboratory approach to diagnosis in Indians. Indian J Pathol Microbiol 2014;57:31-8.  Back to cited text no. 2
Böttiger LE. Heparin-induced thrombocytopenia. Acta Med Scand 1985;218:257-9.  Back to cited text no. 3
Fidlar E, Jaques LB. The effect of commercial heparin on the platelet count. J Lab Clin Med 1948;33:1410-23.  Back to cited text no. 4
Rhodes GR, Dixon RH, Silver D. Heparin induced thrombocytopenia with thrombotic and haemorrhagic manifestations. Surg Gynecol Obstet 1973;136:409-16.  Back to cited text no. 5
Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006;4:759-65.  Back to cited text no. 6
Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: A systematic review and meta-analysis. Blood 2012;120:4160-7.  Back to cited text no. 7
Kapadia FN, Ketkar AS, Deshpande AS, Puri VC, Khodaiji SJ. Evaluation of various laboratory assays in detection of heparin-induced thrombocytopenia in an adult general ICU. Int J Lab Hematol 2013;35:137-43.  Back to cited text no. 8
Napolitano LM, Warkentin TE, Almahameed A, Nasraway SA. Heparin-induced thrombocytopenia in the critical care setting: Diagnosis and management. Crit Care Med 2006;34:2898-911.  Back to cited text no. 9
Bhatt VR, Aryal MR, Shrestha R, Armitage JO. Fondaparinux-associated heparin-induced thrombocytopenia. Eur J Haematol 2013;91:437-41.  Back to cited text no. 10
Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, et al. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost 2016;14:1206-10.  Back to cited text no. 11


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