Given that the 4T scoring system for HIT showed a high probability with 8 points—identified by a platelet count fall > 50%, a platelet nadir > 20,000 cells/mm3, clear onset between days 5 and 14 with exposure to heparin/LMWH, new thrombosis, and no apparent cause of thrombocytopenia—suspicion for HIT remained high. Both functional and immunologic assays were negative for HIT, when repeated 2 weeks apart. The assays for laboratory diagnosis of HIT are immunologic, done by ELISA with a sensitivity of > 95% and a specificity of 50%–89%, and functional, done by SRA with a sensitivity > 90% and a specificity > 90%.2 As neither assay is 100% sensitive and specific, we still had a high clinical suspicion for HIT.
The HIT diagnostics in the presence of other comorbid states that may also induce thrombocytopenia represent a specific clinical problem. Despite increasing awareness of the clinical features of HIT, laboratory detection of the pathogenic HIT antibodies remains central to diagnosis. 4–6 This is because thrombocytopenia during heparin anticoagulation does not necessarily indicate HIT. Indeed, several other disorders complicated by thrombosis and thrombocytopenia during or shortly following heparin treatment strongly resemble HIT.These “pseudo-HIT”disorders7,8 (eg, cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome) can reliably be distinguished from HIT by negative results using sensitive tests for HIT antibodies.
Thrombosis is strongly associated with HIT, with an incidence of 50%– 67%.9,10 The most common complication of HIT is venous thrombosis (DVT being the most frequent, followed by pulmonary embolism).9,11 Arterial thrombosis commonly presents as limb ischemia followed by cerebral vascular accident and myocardial infarction. Our patient had DVT followed by NSTEMI, cerebral vascular accident, and pulmonary embolism. He also had splenic and renal infarctions, which are rare in HIT. A literature review revealed, in abstract form, a retrospective study from a single institution showing a high incidence of thrombosis in a patient with a high 4T score and negative SRAs.12
The most common causes of thrombocytopenia in cancer are related to cancer treatment and bone marrow invasion by tumor cells. Chemotherapy and radiation therapy are damaging to the bone marrow and can cause severe myelosuppression, which results in lowering of platelet counts as well as white and red blood cell counts. It commonly occurs in patients with leukemia and lymphoma, but there are many other cancer types that can spread to bone marrow. Other causes of thrombocytopenia in cancer include the syndrome of disseminated intravascular coagulation and thrombotic microangiopathy.13
Nonbacterial thrombotic endocarditis (NBTE) is a disease characterized by the presence of vegetations on cardiac valves, consisting of fibrin and platelet aggregates devoid of inflammation or bacteria. NBTE has increasingly been recognized as a condition associated with numerous diseases and a potentially life-threatening source of thromboembolism. NBTE is not a common entity; however, it is frequently underestimated, probably due to underlying diseases (cancer, autoimmune disorders, HIV). NBTE is difficult to diagnose and relies on strong clinical suspicion. NBTE is also difficult to manage, and each case should be individually managed by identifying and treating the underlying pathology.14 Even though our patient had thromboembolism, there was no evidence of vegetations on cardiac valves by transthoracic or transesophageal echocardiography.
Trousseau’s syndrome is a paraneoplastic syndrome characterized by hypercoagulability related to malignancy. Coagulation abnormalities may include disseminated intravascular coagulation, pulmonary embolism, various types of gangrene, thrombotic endocarditis, arterial thrombosis, and embolic stoke.15 We considered this with our patient; however, a literature review showed no cases of Trousseau’s syndrome associated with thrombocytopenia, although concurrent Trousseau’s syndrome and HIT could not be excluded.
In summary, we need to consider all the above differential diagnoses in a patient presenting with thrombocytopenia and thrombosis. Treatment relies on clinical correlation of all the findings and supporting data.