Indian Journal of Critical Care Case Report
Volume 2 | Issue 6 | Year 2023

HIT Syndrome Complicating Severe ARDS Requiring VV ECMO: A Case Report

Ranjana Venkatachalapathy1, Ganshyam Jagathkar2, Chandreshkumar Sudani3

1–3Department of Critical Care Medicine, Medicover Hospital, Hyderabad, Telangana, India

Corresponding Author: Ranjana Venkatachalapathy, Department of Critical Care Medicine, Medicover Hospital,Hyderabad, Telangana, India, Phone: 9677077945, e-mail:

Received on: 02 March 2023; Accepted on: 19 October 2023; Published on: 01 December 2023


Background: Extracorporeal membrane oxygenation (ECMO) is a lifesaving intervention for patients with refractory respiratory failure and/or shock and can be provided via a venovenous (VV) or venoarterial (VA) circuit. Application of ECMO exposes the patient to a number of complications ranging from hemorrhage to infection. Thrombocytopenia is one such complication. Due to the need for systemic anticoagulation with unfractionated heparin (UFH), those treated with ECMO may be at risk for heparin-induced thrombocytopenia (HIT). Incidence of HIT in ECMO is <1%. Being a rare entity, HIT syndrome in ECMO presents as a unique diagnostic and therapeutic challenge.

Case description: A 45-year-old male, a known smoker, presented to the hospital with complaints of fever and cough for 1 week and grade 4 breathlessness for 1 day. He was diagnosed as acute respiratory distress syndrome (ARDS) with H1N1 positive, and treatment was initiated accordingly. However, during the course of his stay in the intensive care unit (ICU), his oxygenation worsened. He was upgraded to high-flow nasal cannula (HFNC) support but had to be eventually intubated and mechanically ventilated as his respiratory mechanics were not improving. In view of refractory hypoxemia, VV ECMO was initiated with heparin infusion on flow. Initially, an improvement in oxygenation was witnessed, but 2 days post initiation of ECMO, complications raised in the form of thrombocytopenia, recurrent oxygenator failure (clotting), and deep vein thrombosis (DVT) of the right femoral vein. Even though initial suspicion was of sepsis-induced thrombocytopenia, the presence of thrombosis with 4T score of 7 strongly favored HIT syndrome, and diagnosis was confirmed by laboratory testing. Immediately, the circuit and oxygenator were changed, and heparin infusion was replaced with bivalirudin infusion. The patient developed ventilator-associated pneumonia as well as transfusion-related acute lung injury (TRALI) due to multiple transfusions. Antibiotics were escalated accordingly, and he underwent tracheostomy, anticipating prolonged ventilator period. Slowly, his oxygenation improved. After 28 days of VV ECMO, he was weaned off the ventilator and ECMO and was discharged home.

Conclusion: The challenges faced in this case drive home the fact that HIT syndrome must be the first among the differentials when a patient on ECMO develops thrombocytopenia, and the timely diagnosis and management of HIT are very crucial for a good outcome.

How to cite this article: Venkatachalapathy R, Jagathkar G, Sudani C. HIT Syndrome Complicating Severe ARDS Requiring VV ECMO: A Case Report. Indian J Crit Care Case Rep 2023;2(6):172–175.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.

Keywords: Acute respiratory distress syndrome, Case report, Extracorporeal membrane oxygenation, Heparin-induced thrombocytopenia


A 45-year-old male patient with no comorbidities presented to the hospital with complaints of fever and cough for 1 week and breathlessness for 2 days, which had aggravated from grade 2 to grade 4 within 1 day. He was a known smoker for 10 years. On presentation, his room air saturation was 78%, which improved to 100% with oxygen support at 4 L/minute. Swabs for reverse transcription polymerase chain reaction (RT-PCR) and H1N1 were sent, and he was shifted to intensive care unit (ICU) for further management. Computed tomography (CT) chest was done, which revealed multiple ground-glass opacities not confined to peripheries. He was afebrile on arrival; total leukocyte counts were 4100, and platelet count was 227,000. He was initiated on treatment with antibiotics, antivirals, and nebulization along with oxygen support while awaiting reports. Subsequently, his swab for H1N1 came positive. He was started on oseltamivir tablet (75 mg twice a day). However, his oxygen requirement slowly increased with decreasing PaO2/FiO2 (P/F) ratios and increasing carbon dioxide retention. He was upgraded to high-flow nasal cannula (HFNC) support but had to be eventually intubated and mechanically ventilated as his respiratory mechanics were worsening. Prone ventilation was also tried for him in view of P/F ratios decreasing below 150. With no improvement in his oxygenation, venovenous (VV) extracorporeal membrane oxygenation (ECMO) was planned for him. VV ECMO was initiated for him with 2500 revolutions per minute (RPM) FiO2 of 100%, and sweep gas flow of 3.5 L/minute (Fig. 1). He was on infusions of heparin and fentanyl. Activated clotting time (ACT) was checked second hourly to titrate heparin infusion. ACT target was 160–180 (Fig. 2). Daily complete blood profile, renal function tests, prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) were also assessed. His oxygenation started improving on initiation of ECMO. However, on the third day of ECMO, white clots were noticed in his oxygenator, and postmembrane oxygenation was poor, leading to desaturation and increased FiO2 requirements. There was no improvement in his oxygenation even after increasing the LRPM and sweep gas flows. Lab values revealed that platelet counts had decreased from 2 lakhs to 175,000. Sepsis-induced thrombocytopenia was suspected, and tropical fever workup was also done. The oxygenator was subsequently changed 1 day later after noticing blood clots through transparent surface of oxygenator (Fig. 3). On the fifth day of ECMO, the second oxygenator also showed the presence of tiny blood clots within it. However, this time, we noticed that his platelet counts had dropped significantly from 175,000 to 1 lakh to 50,000, and the patient had also developed deep venous thrombosis of his right lower limb extending into the internal iliac veins. Hence, heparin-induced thrombocytopenia (HIT) was strongly suspected. 4T score was 7, indicating a high probability for HIT, and laboratory workup for HIT was done. The second oxygenator was also changed. Our patient tested positive for HIT antibodies 2 days later. In these 2 days, his platelets continued to drop, leading to multiple random donor platelets (RDP) transfusions (Fig. 4). Immediately, the circuit and oxygenator were changed again, and heparin infusion was replaced with bivalirudin infusion at 0.1 mg/kg/hour. Bivalirudin infusion was titrated with (twice daily monitoring of APTT values, which was targeted to 2–2.5 times control, and second hourly monitoring of ACT, which was targeted around 160–200 (Fig. 5). The management was further complicated with the patient developing ventilator-associated pneumonia with polymicrobial growth tested on bronchi alveolar lavage samples. The patient also developed transfusion-related acute lung injury (TRALI) due to eight random donor platelets transfusions (Fig. 6). This led to increased oxygen requirements, which made changing the oxygenator more challenging, almost resulting in a near cardiac arrest situation. Antibiotics were escalated accordingly, and he underwent tracheostomy anticipating prolonged ventilator period. Slowly, his oxygenation improved, and we were able to bring down his FiO2 requirements to 30% and bring down the sweep gas flows to 1.5 L/minute. After 28 days of VV ECMO, we were able to wean him off the ventilator and ECMO (Fig. 7). However, the decannulation of ECMO was complicated by the presence of a deep vein thrombosis (DVT) in the right femoral vein where the venous cannula was present. To prevent the complications anticipated from dislodgement of the cannula upon removing it, an inferior vena cava (IVC) filter was secured. Throughout his stay in the hospital, the patient did not develop any kidney injury, and his renal function tests remained normal. Subsequently, the patient was decannulated of the tracheostomy as well, and he was discharged home on tablet apixaban 5 mg twice a day.

Fig. 1: Patient on ECMO

Fig. 2: Heparin dose titration as per ACT levels

Fig. 3: Clots seen inside oxygenator

Fig. 4: Trend of change in platelet counts during ECMO

Fig. 5: Bivalirudin dose titration as per ACT levels

Fig. 6: Worsening infiltrates on chest X-ray

Fig. 7: Resolution of infiltrates on chest X-ray


Extracorporeal membrane oxygenation (ECMO) has been proven to be a lifesaving circulatory support in critically ill patients with respiratory and cardiac failure. However, the continuous interaction between the blood and the extracorporeal circuit poses a high risk of thrombotic complications in patients on ECMO. Hence, anticoagulation is necessary. Unfractionated heparin (UFH) is the first choice for systematic anticoagulation as it is inexpensive, easily titratable, and reversible by protamine.1

Thrombocytopenia occurs commonly in patients on ECMO. The various causes are sepsis, bleeding, drugs, hemodilution, circuit-related causes, and HIT. HIT is unique because it is an immunologic reaction to heparin. Antibodies are formed to a complex of heparin and platelet factor 4, which in turn activates platelets. This leads to the release of procoagulant particles, thrombocytopenia, generation of thrombin, and thrombosis.2 HIT occurs in approximately 0.5% of patients with inconsequential exposure to heparin, such as catheter flushes, 0.1–1% of patients treated with low-molecular-weight heparin (LMWH), and 3–5% of patients who are on UFH. The incidence of HIT in ECMO is reportedly <1%.

A high index of suspicion and the use of predictability scores such as the HIT expert probability score, post-cardiopulmonary bypass (CPB) score, and, more commonly, the 4T score is required to diagnose HIT. In our case, HIT was suspected with high probability, based on a 4T score of 7. It is recommended that a high 4T score mandates laboratory testing.3

Here, HIT was confirmed by the immunoglobulin G-enzyme-linked immunosorbent assay (IgG-ELISA) technique. ELISA was the first widely available technique and was recommended as the first-line laboratory test by American Society of Hematology (ASH) guidelines.4 In a 2017 review, Arepally mentioned that anti-PF4/H IgG antibodies are the most appropriate isotype for HIT.4

The key aspects of HIT management include immediate cessation of heparin and the introduction of nonheparin anticoagulants, such as argatroban or bivalirudin (direct thrombin inhibitors), or danaparoid or fondaparinux (factor Xa inhibitors).

In this case, we used bivalirudin as an alternative anticoagulant. The advantages of using bivalirudin are—only 20% has renal clearance, 80% has proteolytic elimination and direct suppression of thrombin and collagen-induced platelet procoagulant activity, and a short t1/2 of only 25 minutes.5 The efficacy of bivalirudin can be monitored by ACT and APTT, which show a good correlation. It has been reported that there is no risk of HIT from bivalirudin.6 The incidences of bleeding events in patients receiving bivalirudin and in those receiving UFH were comparable, but there were no bleeding complications with our patient. One of the major issues with direct thrombin inhibitors is “APTT-confounding.” It is reported that in the presence of factors influencing prothrombin, such as coagulopathy secondary to disseminated intravascular coagulation (DIC), liver dysfunction, hemodilution, and consumption of coagulation factors 11 and 12 on extracorporeal circuits, APTT might show false high values, which may lead to drug underdosing.7 Thus, it is better to target a higher range of ACT values and APTT 2–2.5 times control as we have done with our patient. There are not many studies on the optimal dosing of bivalirudin on ECMO patients with HIT. There are large variations in bivalirudin dosing ranging from 0.05 mg/kg/hour to 1.75 mg/kg/hour with or without loading dose. A lot of factors such as anticoagulation target, ECMO indication, institution protocols, and renal function may be the reason for this heterogeneity. Therefore, careful monitoring and titration are required in such patients.8 There are no guidelines available on titration of heparin or bivalirudin based on ACT levels. In this case, the titration was done as per our discretion, targeting an ACT of 160–180 for heparin and 160–200 for bivalirudin.

After a total ECMO duration of 28 days, decannulation was complicated by the presence of deep venous thrombosis in the right femoral vein, which was the site of cannulation extending into the external iliac vein. Deep venous thrombosis is a known complication of ECMO due to prolonged periods of in situ cannulas, and there is a high risk of massive pulmonary embolism during decannulation.9 Placement of an IVC filter prior to decannulation can prevent this complication.


There has been an increasing trend in the usage of ECMO for refractory hypoxia. ECMO is often accompanied by its own set of complications, one of which is thrombocytopenia. This case highlights the importance of having a high degree of suspicion of HIT when a patient on ECMO develops thrombocytopenia or thrombotic manifestations. The timely diagnosis of HIT syndrome is a game changer in the management of ECMO and leads to a drastic improvement in patient outcomes.


Ranjana Venkatachalapathy

Ganshyam Jagathkar

Chandreshkumar Sudani


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