Heparin induced thrombocytopenia
Types
Type 2 HIT is an immune-mediated disorder that typically occurs 4-10 days after exposure to heparin and has life- and limb-threatening thrombotic complications. In general medical practice, the term HIT refers to type 2 HIT.
HIT must be suspected when a patient who is receiving heparin has a decrease in the platelet count, particularly if the fall is over 50% of the baseline count, even if the platelet count nadir remains above 150 x 109/L. Clinically, HIT may manifest as skin lesions at heparin injection sites or by acute systemic reactions (eg, chills, fever, dyspnea, chest pain) after administration of an intravenous bolus of heparin.
Unlike other forms of thrombocytopenia, HIT is generally not marked by bleeding; instead, venous thromboembolism (eg, deep venous thrombosis, pulmonary embolism) is the most common complication. Less often, arterial thrombosis (eg, myocardial infarction) may occur. For that reason, the disorder is sometimes termed heparin-induced thrombocytopenia and thrombosis (HITT).
Diagnosis of HIT is based on the combination of clinical findings, thrombocytopenia characteristics, and laboratory studies of HIT antibodies. Treatment of HIT begins with discontinuation of all heparin products (including heparin flushes of intravenous catheters). The patient should then be started on an alternative anticoagulant 1).
The incidence of heparin induced thrombocytopenia (HIT) in neurological patients continues to increase with expansion of indication for neurointerventional procedures. The pathophysiology of HIT is related to a hypersensitivity reaction against complex platelet factor 4. The diagnosis is mostly clinical and is often confirmed by laboratory testing. Patients with HIT have a higher rate of thromboembolic complications, both arterial and venous, and with worse neurological outcomes at the time of discharge. Early diagnosis and heparin cessation are essential in the management of those patients. Both immediate and prolonged alternative anticoagulation are necessary. Understanding of the mechanism of action, indication and drug interaction of the alternative anticoagulants (direct thrombin inhibitors, fondaparinux and danaparoid) and warfarin is essential during management of these patients 2).
Venous thromboembolism (VTE) is associated with heparin induced thrombocytopenia (HIT) infrequently (< 1%) in low molecular weight heparin (LMWH) treated patients, yet often (approximately one in eight cases) in unfractionated heparin-treated patients. Physicians should suspect the possibility of HIT if VTE develops during or soon after unfractionated heparin use; if thrombocytopenia is present, alternative anticoagulation should be used until HIT is excluded 3).
Heparin-induced thrombocytopenia type II correlates with a worse outcome and higher risk of thromboembolic complications in aneurysmal subarachnoid hemorrhage patients. In addition, HIT II was strongly associated with the number of angiographic procedures performed during the same hospitalization 4).
The presence of HIT in SAH has adverse consequences and is more likely in female patients who have undergone aneurysm clipping and require multiple endovascular vasospasm treatments 5).
SAH patients with isolated heparin induced thrombocytopenia and heparin induced thrombocytopenia with thrombotic syndrome did not differ in the incidence of new thromboses, incidence of hemorrhage, or hospice/death. Patients with isolated heparin induced thrombocytopenia had fewer “poor treatment-related effects” than heparin induced thrombocytopenia with thrombotic syndrome patients 6).
Studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment.
Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold 7).
Case series
Fifty-nine patients (15%) met the clinical diagnostic criteria for HIT II. The average platelet count nadir in the HIT II patients was 68,600 +/- 25,300/microl (mean +/- standard deviation). Female patients and patients with Fisher Grade 3 were more likely to develop HIT II (P < 0.01). Thirty-six patients (61%) underwent a neuroendovascular procedure. The rate of systemic thrombotic complications in the HIT II patients was 37 versus 7% in SAH patients without HIT II (P < 0.001), and the rate of new hypodensities on head computed tomographic scans was 66% in the HIT II patients versus 40% in the SAH patients without HIT II (P < 0.001). Clinical outcomes were worse in the HIT II patients. The outcome was favorable for 38% in the HIT II patients versus 52% in all SAH patients (P < 0.05), and deaths were more common (29%) in the HIT II patients than in all SAH patients (12%, P < 0.001).
The incidence of HIT II in SAH patients at a single center was 15%. The SAH patients with HIT II had significantly higher rates of thrombotic complications, new hypodensities on head computed tomographic scans, more deaths, and significantly less favorable outcomes. This is the first report of the incidence of HIT II in a neurosurgical patient population 8).
Case reports
2013
The endarterectomy was successfully performed while the patient received argatroban, both as a continuous infusion and intermittent irrigation during dissection of the plaque. Postoperatively, the drip was continued for 24 hours, and the patient was discharged day 2 on a daily dose of 325 mg of aspirin. At the 6-month examination, Doppler ultrasound revealed normal anterograde velocities with no evidence of stenosis, and the patient noted no subsequent ischemic events.
Serrone et al., now recommend systemic intravenous and local argatroban irrigation to prevent thromboembolic complications in CEA cases with HIT and renal insufficiency. Bivalirudin for both systemic intravenous use and local irrigation may be safer in patients without renal insufficiency because of its shorter half-life 9).
2012
2011
A case of bifrontal intracerebral haemorrhage in a patient with heparin-induced thrombocytopenia type II (HIT II). HIT II was induced by treatment with low-molecular-weight heparin for recurrent deep vein thrombosis caused by essential thrombocytosis and accompanied by hepatic thromboembolism. This patient was treated with platelet substitution and neurosurgical haematoma evacuation. Anticoagulation with 2500 units danaparoid per day was sufficient for therapy of thrombosis and no rebleeding occurred 12).
A 61-year-old woman treated for cerebral venous thrombosis (CVT) leading to diagnosis of essential thrombocythemia (ET). During treatment with unfractionated heparin, after initial improvement of clinical state, signs of cerebral hypertension reappeared. Although the platelet count decreased, heparin-induced thrombocytopenia (HIT) was only suspected 2 days later when it dropped below the standard 150 × 10(9) L(-1) threshold. HIT diagnosis was confirmed by the presence of anti-PF4/heparin IgG. This late finding was the cause of the extension of CVT with worsening of cerebral hypertension necessitating decompressive craniectomy. Elevated basal platelet count due to ET can delay diagnosis and treatment of HIT. In this case, physicians should be more attentive to platelet count variations rather than thrombocytopenia threshold 13).
2009
A case of intratumor haemorrhage in the cavernous sinus 1 week after cardiac surgery. The pathogenesis may be venous thrombosis and haemorrhagic infarct caused by HIT following cardiopulmonary bypass surgery 15).