The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study

In contrast with extensive documentation in patients treated with unfractionated heparin (UFH), the incidence of heparin-induced thrombocytopenia (HIT) in medical patients receiving low-molecular-weight heparin (LMWH) is less well defined. In a prospective cohort study, the platelet count was monitored in 1754 consecutive patients referred to 17 medical centers and treated with LMWH for prophylaxis or treatment of thromboembolic disorders. The diagnosis of HIT was accepted in case of a platelet drop of at least 50%, the absence of obvious explanations for thrombocytopenia, and the demonstration of heparin-dependent IgG antibodies. HIT developed in 14 patients (0.80%; 95% CI, 0.43%-1.34%), in all of them within the first 2 weeks, and was more frequent in patients who had (1.7%) than in those who had not (0.3%) been exposed to UFH or LMWH (OR = 4.9; 95% CI, 1.5-15.7). The prevalence of thromboembolic complications in HIT patients (4 of 14; 28.6%) was remarkably higher than that (41 of 1740; 2.4%) observed in the remaining patients (OR = 16.6; 95% CI, 5.0-55.0). Immune thrombocytopenia and related thromboembolism may complicate the clinical course of medical patients treated with LMWH with a frequency that is not different from that observed with the use of UFH. The previous administration of heparin increases the rate of HIT.     

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating complication of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Our objective was to determine and compare the incidences of HIT in surgical and medical patients receiving thromboprophylaxis with either UFH or LMWH. All relevant studies identified in the MEDLINE database (1984-2004), not limited by language, and from reference lists of key articles were evaluated. Randomized and nonrandomized controlled trials comparing prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes were included. Two reviewers independently extracted data on thromboprophylaxis (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay, and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic events. HIT was defined as a decrease in platelets to less than 50% or to less than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287 patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT (1014 patients), 3 prospective studies (1464 patients) with nonrandomized comparison groups in which HIT was appropriately measured in both groups, and 10 RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were performed using a random effects model and favored the use of LMWH: (1) RCTs measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI], 0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10 (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the risk was 2.6%. Most studies were of patients after orthopedic surgery.     

Spontaneous heparin-induced thrombocytopenia syndrome without any proximate heparin exposure,infection, or inflammatory condition: Atypical clinical features with heparin-dependent platelet activating antibodies

Recent studies suggest that a thromboembolic disorder resembling heparin-induced thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients without any history of heparin exposure. It is likely due to anti-platelet factor 4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial surfaces and nucleic acids. We describe an atypical case of spontaneous HIT syndrome. A 70-year-old man suddenly presented with acute cerebral sinus thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for the treatment of CST, his platelet count fell precipitously and he developed deep vein thrombosis, a clinical picture consistent with rapid-onset HIT but without any proximate episodes of heparin exposure, infection, trauma, surgery, or other acute illness. Antigen assays and a washed platelet activation assay indicated that the patient already possessed anti-PF4/heparin IgG antibodies with heparin-dependent platelet activation properties on admission. Cessation of UFH and initiation of argatroban resulted in prompt recovery of his platelet count without further thromboembolic events. We identified two similar cases in the literature. However, these patients do not meet the recently proposed criteria for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or delayed diagnosis of HIT appears to be associated with worse outcomes. We propose that these atypical cases should be included in the category of spontaneous HIT syndrome.     

Heparin-induced thrombocytopenia: 2008 update

Opinion statement Unfractionated heparin (UFH) and the low molecular weight heparin (LMWH) preparations are two of the most commonly prescribed medications in the hospital, and indications for their use are increasing. An increasingly recognized untoward effect of either UFH or LMWH is heparin-induced thrombocytopenia (HIT), a transient, prothrombotic condition that may result in venous or arterial thrombosis and amputation or death. This immune-mediated process generally develops within 4 to 14 days of administration, although it may occur more rapidly if there has been a recent exposure; it may even occur days to weeks after UFH or LMWH has been discontinued. Although once considered necessary for the diagnosis of HIT, thrombocytopenia is no longer essential. A 50% reduction in the platelet count from pre-heparin treatment levels is now considered a more specific finding. Prompt recognition, discontinuation of the offending agent, and initiation of an alternative anticoagulant are essential for prevention and/or treatment of these potentially devastating complications.     

The management of heparin-induced thrombocytopenia

The Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology has produced a concise practical guideline to highlight the key issues in the management of heparin-induced thrombocytopenia (HIT) for the practicing physician in the UK. The guideline is evidence-based and levels of evidence are included in the body of the article. All patients who are to receive heparin of any sort should have a platelet count on the day of starting treatment. For patients who have been exposed to heparin in the last 100 d, a baseline platelet count and a platelet count 24 h after starting heparin should be obtained. For all patients receiving unfractionated heparin (UFH), alternate day platelet counts should be performed from days 4 to 14. For surgical and medical patients receiving low-molecular-weight heparin (LMWH) platelet counts should be performed every 2-4 d from days 4 to 14. Obstetric patients receiving treatment doses of LMWH should have platelet counts performed every 2-4 d from days 4 to 14. Obstetric patients receiving prophylactic LMWH are at low risk and do not need routine platelet monitoring. If the platelet count falls by 50% or more, or falls below the laboratory normal range and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration HIT should be considered and a clinical assessment made. If the pretest probability of HIT is high, heparin should be stopped and an alternative anticoagulant started at full dosage unless there are significant contraindications while laboratory tests are performed. Platelet activation assays using washed platelets have a higher sensitivity than platelet aggregation assays but are technically demanding and their use should be restricted to laboratories experienced in the technique. Non-expert laboratories should use an antigen-based assay of high sensitivity. Only IgG class antibodies need to be measured. Useful information is gained by reporting the actual optical density, inhibition by high concentrations of heparin, and the cut-off value for a positive test rather than simply reporting the test as positive or negative. In making a diagnosis of HIT the clinician's estimate of the pretest probability of HIT together with the type of assay used and its quantitative result (enzyme-linked immunosorbent assay, ELISA, only) should be used to determine the overall probability of HIT. Clinical decisions should be made following consideration of the risks and benefits of treatment with an alternative anticoagulant. For patients with strongly suspected or confirmed HIT, heparin should be stopped and full-dose anticoagulation with an alternative, such as lepirudin or danaparoid, commenced (in the absence of a significant contraindication). Warfarin should not be used until the platelet count has recovered. When introduced in combination with warfarin, an alternative anticoagulant must be continued until the International Normalised Ratio (INR) is therapeutic for two consecutive days. Platelets should not be given for prophylaxis. Lepirudin, at doses adjusted to achieve an activated partial thromboplastin time (APTT) ratio of 1.5-2.5, reduces the risk of reaching the composite endpoint of limb amputation, death or new thrombosis in patients with HIT and HIT with thrombosis (HITT). The risk of major haemorrhage is directly related to the APTT ratio, lepirudin levels and serum creatinine levels. The patient's renal function needs to be taken into careful consideration before treatment with lepirudin is commenced. Severe anaphylaxis occurs rarely in recipients of lepirudin and is more common in previously exposed patients. Danaparoid in a high-dose regimen is equivalent to lepirudin in the treatment of HIT and HITT. Danaparoid at prophylactic doses is not recommended for the treatment of HIT or HITT. Patients with previous HIT who are antibody negative (usually so after >100 d) who require cardiac surgery should receive intraoperative UFH in preference to other anticoagulants that are less validated for this purpose. Pre- and postoperative anticoagulation should be with an anticoagulant other than UFH or LMWH. Patients with recent or active HIT should have the need for surgery reviewed and delayed until the patient is antibody negative if possible. They should then proceed as above. If deemed appropriate early surgery should be carried out with an alternative anticoagulant. We recommend discussion of these complex cases requiring surgery with an experienced centre. The diagnosis must be clearly recorded in the patient's medical record.     

Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia.

BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH.     

ET gets HIT--thrombocytotic heparin-induced thrombocytopenia (HIT) in a patient with essential thrombocythemia (ET).

Immune-mediated heparin-induced thrombocytopenia (HIT) is a relatively common complication in patients receiving heparin, and represents a strong risk factor for thromboembolic disease associated with high morbidity and mortality. The condition is commonly defined as a platelet count fall of greater than 30-50% to values below 150 x 10(9)/l. Despite this, several cases with platelet count nadirs in the normal range have been reported. This report describes a patient with status post-carotid thrombendarterectomy presenting with neurological symptoms and thrombocytosis (1235 x 10(9)/l), which in due course was diagnosed to be caused by essential thrombocythemia (ET). Heparin therapy was established and symptoms resolved markedly. After 5 days of standard heparin therapy, serologically confirmed HIT with new neurological symptoms occurred. The platelet count nadir attributed to HIT was far above normal (633 x 10(9)/l), which nevertheless represented a substantial relative platelet count fall (49%). This is the first reported case of serologically confirmed HIT in a patient with ET. Furthermore, it represents the first published case of HIT being present in thrombocytosis. Clinicians should be aware that atypical HIT can even be present in thrombocytosis and, because of nomenclature, HIT with normal and elevated platelet count nadirs is likely to be largely underdiagnosed.     

Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy

BACKGROUND: Despite widespread heparin use in clinical practice, the associated development of thrombocytopenia is an underrecognized and undertreated complication. METHODS: We analyzed data from consecutive hospitalized patients treated with heparin (unfractionated or low molecular weight) for 4 days or longer to determine the incidence, predictors, prognostic significance, and management of "thrombocytopenia," defined as a platelet count less than 150 x 10(9)/L, reduction in platelet count of 50% or more from the admission level, or both. RESULTS: We enrolled 2420 patients (median age, 65.2 years; 43.8% women) in 48 US hospitals. Thrombocytopenia occurred in 881 patients (36.4%; 95% confidence interval [CI], 34.5%-38.3%). Of those who developed thrombocytopenia, 5.1% died, compared with 1.6% of those without thrombocytopenia (odds ratio [OR], 3.4; 95% CI, 2.1-5.6; P< .001). Thrombocytopenia was also associated with greater risk of myocardial infarction (OR, 2.1; 95% CI, 1.5-2.8; P< .001) and congestive heart failure (OR, 1.3; 95% CI, 1.1-1.6; P= .01). After adjustment for important covariates, thrombocytopenia remained an independent predictor of thrombotic and hemorrhagic events. A relative reduction in platelet count of more than 70% was the strongest independent predictor of death (OR, 13.4; 95% CI, 6.5-27.6; P< .001), followed by a relative reduction in platelet count of 50% to 70%, worse Killip class, occurrence of thromboembolic complications, older age, and longer duration of heparin therapy. CONCLUSIONS: Thrombocytopenia occurs frequently after prolonged heparin therapy and is strongly associated with worse short-term clinical outcome. The relative reduction in platelet count is a powerful independent predictor of all-cause mortality in hospitalized patients.     

Heparin-induced thrombocytopenia

Hemorrhage is the most common and best-recognized complication of heparin treatment. However, a potentially more dangerous complication is the development of heparin-induced thrombocytopenia (HIT). All patients exposed to heparin, irrespective of the dose and route of administration, are at risk of developing HIT. It is due to the formation of antibodies against the heparin-platelet factor 4 complex, which cause secondary activation of platelets, coagulation and, finally, increased thrombin production. The main symptom is the sudden onset of thrombocytopenia involving a drop in the platelet count to less than 50% of the basal level, with or without the appearance of thrombotic complications some 5 to 14 days after the start of heparin therapy. Heparin-induced thrombocytopenia can be detected early in patients receiving heparin by monitoring the platelet count. Demonstration of heparin-dependent platelet activation using an antigen or functional assay confirms the clinical diagnosis. Once the diagnosis of HIT has been confirmed serologically or there is a high level of suspicion of HIT, heparin must be suspended and treatment with an alternative anticoagulant should be considered. This review contains a discussion of the diagnosis and treatment of this syndrome.     

The use of direct thrombin inhibitors in cardiovascular surgery in patients with heparin-induced thrombocytopenia

One of the most important adverse drug reactions that physicians encounter is the life- and limb-threatening prothrombotic syndrome known as heparin-induced thrombocytopenia (HIT). Unfractionated heparin (UFH), administered during cardiopulmonary bypass (CPB), is highly immunogenic. Heparin-dependent antibodies can develop in 25 to 50% of UFH-treated cardiac surgery patients within 5 to 10 days. These antibodies can activate platelets and are considered the causative agents of HIT. HIT is a relatively common complication, occurring in 1 to 3% of cardiovascular surgery patients when UFH administration is continued postoperatively. It is strongly associated with new thromboembolic events leading to limb amputation and death. In acute or recent (< 100 days) HIT, alternative anticoagulatory regimens are needed during CPB surgery for prevention of HIT-related thrombosis. Treatment options for such patients now generally include the use of alternative anticoagulants such as lepirudin, bivalirudin, or danaparoid, as well as a combined treatment with platelet-function inhibitors and heparin. In patients with a history of HIT and no detectable antibodies, heparin is currently the safest approach for high-dose anticoagulation during CPB. Before and after surgery, however, alternative anticoagulants should be used. The risk of clinical HIT after heart surgery could potentially be reduced by using low-molecular-weight heparins for postsurgery anticoagulation.     

Lethal heparin-associated pulmonary embolism--case reports

Thrombocytopenia is a known adverse reaction occurring in some patients receiving heparin. Two different types of heparin-induced thrombocytopenia have been described. Heparin-induced thrombocytopenia type I is a mild thrombocytopenia after 1 to 4 days of heparin therapy, attributed to a direct interaction between heparin and circulating platelets. No specific treatment is necessary. Heparin-induced thrombocytopenia type II is a severe thrombocytopenia mediated by an immunologic mechanism. Type II generally develops after 5 to 10 days of heparin therapy and can be associated with potentially devastating thromboembolic complications. The incidence of heparin-induced thrombocytopenia type II is below 3%. Thromboembolic events are always accompanied by a decrease in the platelet count, however, complications in the absence of absolute thrombocytopenia have been reported. Diagnosis of HIT type II is based on clinical features and laboratory studies for the heparin-dependent platelet antibody. Immediate cessation of heparin administration is essential. Several alternative anticoagulant therapies have been studied and have shown promising results when used for this purpose. Two patients undergoing coronary artery bypass surgery are presented in whom pulmonary embolism developed due to heparin-induced thrombocytopenia type II. In both cases, platelet counts were within the subnormal range at the time of the first thromboembolic complication. The clinical, therapeutic, and prognostic implications are discussed.     

Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low-molecular-weight heparin (LMWH) therapy (LMW-HIT). To define the clinical and biological characteristics of LMW-HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin-platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW-HIT) and 48 with UFH either alone (UF-HIT, n = 34) or combined with LMWH (UF/LMW-HIT, n = 14). The LMW-HIT and UF-HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW-HIT patients compared with UF-HIT patients (P = 0.03). Severe thrombocytopenia (platelets < 15 x 10(9)/l) was more frequent in the LMW-HIT group (P = 0.04). Thrombosis occurred in three of 11 LMW-HIT patients, i.e. as frequently as in UF-HIT patients. LMW-HIT is potentially severe and may be observed after longer heparin treatment compared with UF-HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered.     

Heparin-induced thrombocytopenia: recent experience in a large teaching hospital

Background: Heparin‐induced thrombocytopenia (HIT) is a potentially serious adverse reaction caused by platelet‐activating antibodies. Aim: To describe experience with HIT. Methods: Twenty‐two patients identified by laboratory records of heparin‐associated antibodies with a 50% or greater decrease in platelet count were reviewed in our 600‐bed metropolitan teaching hospital from 1999 to April 2005. Results: There was an increase in the frequency of HIT diagnosed during the review period, which was associated with a rise in the number of requests for HIT antibodies. Thrombotic complications were identified in 14 of 22 patients with HIT. Mean age was 65 years, and 11 patients were men. Seven patients died and HIT was considered contributory in four. One patient required mid‐forearm amputation. Unfractionated heparin was used in all cases and five patients also received enoxaparin. Mean time to HIT screen, reflecting when the diagnosis was first suspected, was 14 days. Platelet nadir ranged from 6 × 10⁹/L to 88 × 10⁹/L, with a percentage drop in platelet count of 67–96%. Alternative anticoagulation (danaparoid) was not used in three patients, two of whom died. Conclusions: HIT is a potentially life‐threatening complication of heparin therapy, associated with a fall in platelet count and a high incidence of thromboembolic complications. It is most frequently seen using unfractionated heparin therapy. The increase in frequency of HIT diagnosed in our hospital appears to be associated with a greater awareness of the entity, although detection is often delayed. Platelet count should be monitored in patients on heparin and the presence of antiplatelet antibodies determined if HIT is suspected. Treatment involves both discontinuation of heparin and the use of an alternative anticoagulant such as danaparoid because of the persisting risk of thrombosis.     

Heparin-induced thrombocytopenia in hemodialysis. Case report and review of the literature

Thrombocytopenia is a potential complication of heparin therapy. There are two forms of heparin-induced thrombocytopenia (HIT). Type-I HIT is characterized by a mild decrease in platelet count that occurs within the first 2-4 days after heparin initiation. The platelet count often returns to normal without stop heparin treatment. The mechanism of thrombocytopenia appears to be due to a direct effect of heparin on platelet activation. The second form (type-II) is an immune-mediated disorder characterized by severe thrombocytopenia, which may include both arterial and venous thrombosis. We present a case of type-II HIT occurred in a hemodialysis patient resulting in acute pulmonary embolism and peripheral venous thrombosis, and review the literature.     

Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of thrombocytopenia: a case report and literature review

Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10⁹/L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient’s serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 10⁹/L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 10⁹/L by POD45 and 199 × 10⁹/L by POD79. The patient’s serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1–1.2 μg/mL, i.e., in vitro fondaparinux “cross-reactivity”). Ultimately, platelet count recovery was associated with seroreversion to a negative SRA (documented at POD151). Our literature review identified joint replacement surgery, specifically knee replacement, to be a relatively common trigger of spontaneous HIT syndrome. Further, including our patient case, 5 of 7 patients with spontaneous HIT syndrome post-orthopedic surgery who received treatment with argatroban developed new and/or progressive lower-limb DVT or recurrent PE despite anticoagulation with this parenteral direct thrombin inhibitor, suggesting that this patient population is at high risk of breakthrough thrombotic events despite treatment with this HIT treatment-approved anticoagulant. Our case also illustrates successful outcome with rivaroxaban for treatment of spontaneous HIT syndrome, consistent with emerging literature supporting safety and efficacy of direct oral anticoagulant therapy for treatment of acute HIT.     

Incidence and clinical relevance of heparin-induced antibodies in patients with deep vein thrombosis treated with unfractionated or low-molecular-weight heparin

The frequency of heparin-induced thrombocytopenia (HIT) varies between different clinical treatment settings and remains unknown for patients treated with unfractionated (UFH) or low-molecular-weight heparin (LMWH) because of deep vein thrombosis. In this multicentre, open-label study, 1137 patients with deep vein thrombosis were randomly assigned to UFH for 5-7 d, reviparin, a LMWH, for 5-7 d (short-treated group) or reviparin for 28 d (long-treated group). Heparin-platelet factor 4 antibodies (HPF4-A) were determined on d 5-7 and d 21. Heparin-induced thrombocytopenia was defined by clinical evaluation. Two patients in the UFH group (incidence: 0.53%, 95% confidence interval (CI): 0.06-1.91) and two patients in the long-treated LMWH group (incidence: 0.53%, 95% CI: 0.06-1.92) had HIT, while no HIT was observed in the short-treated LMWH group. Pulmonary embolism developed in one of the HIT-patients, who had HPF4-A and was treated with UFH. On d 5-7 the incidence of HPF4-A was 9.1% in the UFH group, 2.8% in the short-treated LMWH group and 3.7% in the long-treated LMWH group, with a significant increase to 20.7% in the UFH group and to 7.5% in the long-treated LMWH group on d 21. Therefore the incidence of HPF4-A and heparin-induced thrombocytopenia was lower in patients treated with LMWH compared with UFH for the same duration of treatment.     

Dermatan sulphate in patients with heparin-induced thrombocytopenia

Patients with thromboembolic diseases who develop heparin-induced thrombocytopenia (HIT) type II require an alternative anticoagulation strategy. Dermatan sulphate (DS) was administered to five patients with thromboembolic diseases who developed HIT type II and showed an in vitro cross-reactivity with low molecular weight heparins. The platelet count and the extension of thrombosis were monitored during DS administration. In four of the five patients the platelet count rapidly increased after heparin was discontinued and DS started. A low platelet count persisted in the single patient with cross-reactivity to DS, up to 4 d after its discontinuation. None of the patients experienced thrombus extension, haemorrhagic side-effects or other adverse events.     

Management of anticoagulation in patients with subacute heparin-induced thrombocytopenia scheduled for heart transplantation

Anticoagulation management of patients with recent heparin-induced thrombocytopenia (HIT) requiring cardiopulmonary bypass (CPB) surgery is a serious challenge, and especially difficult in patients requiring urgent heart transplantation. As nonheparin anticoagulants during CPB bear a high risk of major bleeding, these patients are at risk of being taken off the transplant list. Short-term use of unfractionated heparin (UFH) for CPB, with restriction of UFH to the surgery itself, is safe and effective in patients with a history of HIT who test negative for antiplatelet factor 4 (PF4)/heparin antibodies. We present evidence that it is safe to expand the concept of UFH reexposure to patients with subacute HIT (ie, those patients with recent HIT in whom the platelet count has recovered but in whom anti-PF4/heparin IgG antibodies remain detectable) requiring heart transplantation, if they test negative by a sensitive functional assay using washed platelets. This can be lifesaving in patients with end-stage heart failure.     

Prevalence of anti-PF4/heparin antibodies and the HIT syndrome in cardiovascular medicine

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse effect of heparin treatment. HIT is mediated by antibodies directed at complexes that form between heparin and platelet factor 4 in plasma and are located on the platelet surface and on endothelium. HIT occurs in 1 to 2% of patients receiving unfractionated heparin (UFH) and with lower frequency in patients receiving low-molecular-weight heparins and heparinoids. Despite recent insights into the mechanisms of HIT, there remain important unresolved issues. For example, the reason for the wide difference in the frequency of HIT in patients treated with UFH in various clinical trials is not yet clear. There are patient population-dependent differences in the risk for HIT immunoglobulin G and the development of thrombotic episodes. The complex nature of this syndrome may relate to the composition of the responsible antigen. Patients with HIT need a more accurate evaluation of platelet counts and a better assessment of clinical evidence for thrombosis. Alternative anticoagulant therapy approaches are being studied, but there is at this time no firm clinical evidence for which treatment is best for patients with HIT and HIT-related thromboses.     

Cerebral venous thrombosis due to essential thrombocythemia and worsened by heparin-induced thrombocytopenia and thrombosis

This case describes the medical history of 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.