What is the cause of thrombocytopenia in a patient with sickle cell disease (SCD) presenting with acute vaso-occlusive crisis and being treated with enoxaparin (low molecular weight heparin)?

Heparin-Induced Thrombocytopenia (HIT)

The most likely cause of thrombocytopenia in this patient is heparin-induced thrombocytopenia (HIT), given the recent exposure to enoxaparin (a low molecular weight heparin) in the context of acute vaso-occlusive crisis management.

Clinical Reasoning

Why HIT is the Most Likely Diagnosis

The patient received enoxaparin, which directly triggers HIT through antibody formation against platelet Factor 4-heparin complexes. 1 The FDA label explicitly warns that heparin-induced thrombocytopenia is a serious antibody-mediated reaction that occurs in patients treated with heparin, with thrombocytopenia reported at frequencies up to 30%. 1

The timing and platelet count are consistent with HIT. 2 The thrombocytopenia typically occurs 2 to 20 days (average 5 to 9 days) following the onset of heparin therapy, though it can occur earlier if there has been prior heparin exposure within the previous 3 months. 1 The platelet count of 80,000/mm³ falls within the typical HIT range (often between 30,000-70,000/mm³). 2

Applying the 4T Score for HIT

Using the validated 4T scoring system to assess clinical probability: 2

• Thrombocytopenia (T1): Platelet count of 80,000/mm³ with presumed >50% drop from baseline scores 2 points 2
• Timing (T2): Recent enoxaparin exposure during current hospitalization scores 2 points 2
• Thrombosis (T3): No documented thrombosis mentioned scores 0 points 2
• Other causes (T4): Sickle cell disease itself can cause thrombocytopenia, but this is typically mild and associated with splenic sequestration scores 1 point 2

This yields a 4T score of 5 (intermediate to high probability), warranting immediate anti-PF4 antibody testing and discontinuation of heparin. 2

Why Other Diagnoses Are Less Likely

ITP (Immune Thrombocytopenic Purpura)

While one case report suggests SCA may predispose to ITP 3, this is exceedingly rare and would not be the first consideration in a patient with recent heparin exposure. ITP typically presents with more severe thrombocytopenia (<20,000/mm³) and lacks the temporal relationship with heparin administration. 2

HUS (Hemolytic Uremic Syndrome)

The patient has normal creatinine and urea, which essentially rules out HUS. 2 HUS requires evidence of acute kidney injury as a defining feature.

TTP (Thrombotic Thrombocytopenic Purpura)

While TTP can occur in sickle cell patients and presents with thrombocytopenia and hemolytic anemia 4, 5, the absence of neurological symptoms, fever, and the temporal relationship with heparin exposure makes HIT more likely. 2 TTP would also typically present with more severe thrombocytopenia and prominent schistocytes. 4, 5

Thrombocytopenia from Sickle Cell Disease Itself

Mild thrombocytopenia can occur in sickle cell disease through several mechanisms: 2

• Splenic sequestration: Characterized by rapidly enlarging spleen and hemoglobin drop >2 g/dL, with mild to moderate thrombocytopenia 2
• Consumption at sites of vaso-occlusion: Platelets may be consumed during severe vaso-occlusive episodes 6
• Thrombotic microangiopathy: Rare complication presenting with acute chest syndrome, organ failure, and severe hemolysis 5

However, none of these mechanisms explain the temporal relationship with enoxaparin administration as clearly as HIT does.

Critical Management Steps

Immediately discontinue all heparin products (including enoxaparin) if HIT is suspected. 1 The FDA label mandates that if platelet count falls below 100,000/mm³ or recurrent thrombosis develops, heparin must be promptly discontinued and HIT evaluation initiated. 1

Order anti-PF4 antibodies immediately. 2 Immunological tests have excellent negative predictive value and should be performed as soon as possible to guide management. 2

Initiate alternative anticoagulation if HIT is confirmed. 1 Do not use warfarin alone initially, as this can precipitate venous limb gangrene in acute HIT. 2

Important Caveats

Sickle cell patients have competing risks of thrombosis and bleeding. 2, 7 While patients with sickle cell disease have increased risk of venous thromboembolism 2, 7, they also have increased risk of intracranial hemorrhage, making anticoagulation decisions particularly challenging. 7

HIT can occur even after heparin discontinuation. 1 The FDA label warns that HIT or HITT can occur up to several weeks after discontinuation of heparin therapy, so patients presenting with thrombocytopenia or thrombosis after stopping heparin should still be evaluated for HIT. 1

The use of prophylactic anticoagulation in sickle cell disease is controversial. 8 A 2010 review found no compelling data to recommend routine anticoagulation for prevention of vaso-occlusive complications in sickle cell disease, though thromboprophylaxis is recommended for peri- and post-pubertal patients perioperatively. 2, 8