Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin

STUDY OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with a decrease of platelet counts that usually begins after at least 5 days of heparin treatment. Uncertainty exists about the risk of early onset of HIT (ie, < 5 days) in relation to previous heparin exposure. We therefore analyzed the temporal pattern of thrombocytopenia in patients with laboratory-confirmed HIT to assess whether patients with previous heparin exposure have an increased risk of early onset of HIT. DESIGN: Platelet count patterns in patients with a laboratory-confirmed diagnosis of HIT were examined in a retrospective chart review of a clinical study database. The onset of thrombocytopenia < 100 x 10(9)/L associated with the current heparin treatment (mainly unfractionated heparin) was analyzed using nonparametric maximum likelihood estimation. RESULTS: A total of 119 patients with 125 treatment episodes were assessed: HIT developed in 79 patients during initial exposure to heparin, and in 46 patients during reexposure. Early onset (< 5 days) of thrombocytopenia was associated with very recent heparin exposure. Patients reexposed to heparin within 3 months had an earlier onset of thrombocytopenia as compared to patients reexposed to heparin after 3 months (4.9 +/- 4.4 days vs 11.5 +/- 5.5 days [mean +/- SD], p = 0.001). There was no difference between onset on thrombocytopenia < 100 x 10(9)/L in patients reexposed to heparin within 3 to 12 months and after 1 year (9.7 +/- 6.4 days vs 12.3 +/- 5.2 days, p = 0.41). Whether platelet counts were obtained daily or less regularly did not affect the analysis. CONCLUSION: Early onset of thrombocytopenia in HIT is associated with recent heparin treatment (< 3 months). In contrast, for patients who did not receive heparin within the previous 3 months, HIT is an unlikely explanation for thrombocytopenia that occurs within the first 5 days.     

Etiology of thrombocytopenia in all patients treated with heparin products

Abstract:  Purpose : To characterize the cause of thrombocytopenia in all patients treated with heparin products, to determine the incidence of heparin-induced thrombocytopenia (HIT) in unselected hospitalized patients, and to have modern data of the magnitude of this problem. Methods : Retrospective hospital-based cohort study. During a random 2-month period, we reviewed the medical records of all patients treated with heparin agents, screened them for thrombocytopenia, and determined the cause of it. Results : Out of 674 patients who received heparin products, 110 (16%) had thrombocytopenia. The most common causes included cancer chemotherapy, surgery, sepsis, and medications. Three patients met the clinical criteria for HIT. One had antibodies for heparin-platelet factor-4, and received a direct thrombin inhibitor. The other two individuals had a clinical syndrome that resembled immune HIT, but were not tested for HIT antibodies. One suffered a thrombotic episode that led to the death of her fetus. The other died of a possible thromboembolism. Conclusions : This study provides evidence-based data for the differential diagnosis of thrombocytopenia after treatment with heparin products. Our findings suggest that increased awareness of the HIT syndrome might reduce morbidity and mortality. Patients exposed to heparin products, who develop thrombocytopenia, should not be overlooked.     

An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients

BACKGROUND: Diagnosis of immune heparin-induced thrombocytopenia (HIT) is usually based on a fall in platelet count below 150 x 109/L (standard definition of thrombocytopenia). However, this definition may be inappropriate for postoperative patients who often develop postoperative thrombocytosis. We sought to determine an improved definition of thrombocytopenia indicating HIT in postoperative orthopedic patients, including its impact on frequency and thrombotic risk of HIT. METHODS: We performed a secondary analysis of a clinical trial of 665 patients who received unfractionated or low-molecular-weight heparin following elective hip arthroplasty. Daily platelet counts and objective studies for deep vein thrombosis were performed in all patients. Laboratory detection of HIT antibodies from a 362-patient subgroup was used to define sensitivity and specificity of various definitions of thrombocytopenia to indicate HIT. RESULTS: The improved definition of HIT was a 50% or greater platelet count fall from the postoperative peak, as this definition had greater sensitivity (50% vs 25%) and similar high specificity (99.1% vs 99.4%) for detecting HIT-IgG compared with the standard definition. Patients with HIT who were identified using the improved definition had a higher frequency of thrombosis than patients without HIT (72.2% vs 17.3%; P<.001). The improved definition showed an even greater absolute difference in frequency of HIT between unfractionated and low-molecular-weight heparin (4.8% vs 0.6%; P<.001) compared with the standard definition (2.7% vs 0%; P =.002). CONCLUSION: A 50% or greater fall in the platelet count from the postoperative peak is a sensitive definition indicating possible HIT that is associated with an increased risk of thrombosis.     

Risk of thrombosis in patients with malignancy and heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a common immunological drug reaction. After exposure to heparin, some patients develop heparin dependent antibodies with no evidence of thrombosis, while others are at risk of thrombocytopenia, thrombosis, limb loss, and death. We conducted a retrospective chart review on all patients serologically positive for HIT by HPIA ELISA in a single tertiary-care hospital, to determine whether patients with malignancy had an increased risk of thrombotic complications. Medical records of 55 patients who tested positive for HIT and met clinical criteria for HIT were analyzed. All patients had been treated with unfractionated heparin. Malignancy was diagnosed in 11 patients, either at surgery or post-mortem examination. A higher rate of venous thrombosis and pulmonary embolism was observed in patients with HIT and malignant disease when compared to patients with no underlying malignancy (odds ratio 13.6, 95% CI 2.9-63.8).     

Heparin‐induced thrombocytopenia in myeloproliferative disorders: A rare or under‐diagnosed complication?

Patients with myeloproliferative disorders (MPD) are prone to develop thrombotic complications and thus frequently receive heparin. Surprisingly heparin-induced thrombocytopenia (HIT) has been rarely reported in MPD and is potentially under-diagnosed due to the relatively high platelet count. We report three patients with MPD who developed HIT; all presented with a relative fall of platelet counts (although without an absolute thrombocytopenia), thrombosis or skin necrosis and a positive test for HIT antibodies (particle gel immunoassay). Risk factors for developing HIT in our patients were exposure to unfractionated heparin, a recent surgical procedure and female gender. We review the literature on HIT in MPD and discuss the diagnosis of HIT in the absence of an absolute thrombocytopenia.     

Heparin‐induced thrombocytopenia complicating children after the Fontan procedure: Single‐center experience and review of the literature

Heparin‐induced thrombocytopenia (HIT) is a life‐threatening complication of heparin therapy. The risk for HIT correlates with the cumulative dosage of heparin exposure. In Fontan patients, recurrent systemic anticoagulation, traditionally with heparin, is used to alleviate the thrombotic complications that may occur postoperatively when the venous pressure rises and the systemic venous flow into the pulmonary arteries becomes sluggish, putting them at increased risk. As a pressure gradient‐dependent circulation, elevation in systemic venous pressure, most often by venous thrombosis, contributes to circuit failure. Therefore, when HIT complicates patients after the Fontan procedure, it is associated with a high thrombotic morbidity and mortality; thus, a high index of suspicion is mandatory, based on the clinical signs of HIT. It is crucial to intervene early with alternative anticoagulants when HIT is suspected as this step may improve outcome in these patients.     

Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia

Objectives: To correlate optical density and percent inhibition of a two‐step heparin‐induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. Patients and Methods: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 × 10⁹/L) after exposure to heparin, who had a positive two‐step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. Results: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated‐HIT without thrombosis. Eight of the isolated‐HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated‐HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 ± 0.89), including isolated‐HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 ± 0.64) as compared to isolated‐HIT patients who did not develop thrombosis (0.96 ± 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated‐HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8‐fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. Conclusion: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated‐HIT; percent inhibition, however, was not predictive.     

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.     

Diagnosing heparin-induced thrombocytopenia: The need for accuracy and speed

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition resulting from pathogenic antibodies to complexes of heparin and platelet factor 4 (PF4). The diagnosis of HIT can be challenging due to the widespread use of heparin and the frequency of thrombocytopenia in hospitalized patients. Laboratory testing for HIT typically includes an immunoassay to detect antibodies to PF4-heparin and a functional assay. Current HIT diagnostic algorithms recommend using the 4Ts score to determine the need for HIT laboratory testing. Automated calculation of HIT clinical prediction scores in the electronic health record may improve the identification of patients who should undergo HIT testing. Another challenge in the management of patients with suspected HIT is the turnaround time of the laboratory testing needed to confirm the diagnosis. Due to the high daily thrombotic risk of HIT, clinicians must treat patients with intermediate to high pretest likelihood of HIT empirically while awaiting the test results. Treatment for HIT often involves alternative anticoagulants that lack reversal agents, which may increase bleeding risk, prolong hospital stays, and increase costs for patients suspected of having HIT. Rapid immunoassays hold promise to improve the speed of HIT diagnosis. These assays must retain a very high sensitivity for this “can't miss” diagnosis, yet have sufficient specificity to be of diagnostic value. A Bayesian approach has been proposed using two rapid immunoassays in succession, which decreased analytic turnaround time to 60 minutes. Such an approach has the potential to be a much-needed clinical advance in improving accuracy and speed in the diagnosis of HIT.     

Risk of heparin-induced thrombocytopenia in patients receiving thromboprophylaxis

Heparin-induced thrombocytopenia (HIT) is a clinicopathological syndrome associated with heparin therapy that is characterized by a decrease in platelet counts and/or the development of a new thrombosis. Two types of HIT exist, type I is nonimmune and self-resolves, whereas type II is immune-mediated and clinically important. The formation of antibodies against the platelet factor 4-heparin complexes results in platelet activation and thrombin formation, which lead to an increased risk of thrombosis. Unfractionated heparin is associated with a higher risk of HIT than low-molecular-weight heparins. Surgical patients, particularly those undergoing orthopedic or cardiac surgery, are at higher risk of HIT than medical patients. Treatment of HIT involves heparin cessation together with anticoagulation with direct thrombin inhibitors or indirect factor Xa inhibitors.     

Heparin-induced thrombocytopenia in pediatrics.

As in adult patients, heparin is used for prophylaxis and treatment of thromboembolism in newborns, children, and adolescents. Patients receiving heparin are potentially at risk to develop heparin-induced thrombocytopenia (HIT). HIT type II has been extensively described in the adult population; only a few reports address HIT type II in pediatric patients (total of 15 neonates, 4 young children, 12 older children and adolescents). The available data are discussed, and the case of a patient with recurrent thrombosis and HIT type II without thrombocytopenia is presented. The review of the literature reveals that HIT type II occurs especially in neonates and adolescents, corresponding to the two age peaks of thrombosis in pediatric patients. Risk factors for thrombosis include hereditary factors, immobilization, and surgery. HIT complications are severe and partly lead to life-threatening thromboembolism. In three patients, an increasing heparin demand was found. In five cases, thrombocytopenia was absent. Heparin was replaced mostly by danaparoid sodium; in three patients hirudin was used as an alternative anticoagulant. HIT type II represents a potentially dangerous complication of heparin therapy in pediatric patients and should be taken into consideration whenever heparin is given for prophylactic or therapeutic use in newborns, children, or adolescents.     

Heparin-induced thrombocytopenia with thrombosis: Incidence,analysis of risk factors,and clinical outcomes in 108 consecutive patients treated at a single institution

Heparin-induced thrombocytopenia with thrombosis (HITT) can lead to serious morbidity and may be potentially fatal. We reviewed our experience with this entity over a 4-year period, to determine the following: 1) incidence and type of thrombosis in patients with heparin-induced thrombocytopenia (HIT), 2) clinical consequences of thrombosis, i.e., amputation, cerebrovascular accidents and death, 3) risk factors associated with development of thrombosis, and 4) impact of therapy on clinical outcomes in patients with HITT. Between 1991–1994, 108 patients were diagnosed to have HIT by heparin-induced platelet aggregation test. Thirty-two (29%) of these developed thrombotic complications, of which 20 were venous, 8 arterial, and 4 both. Five of the 32 died, 3 underwent amputations, and 3 had cerebrovascular accidents. The patients who developed thrombotic complications, when compared to those with HIT alone, were older (68.7 ± 11.5 vs. 63.3 ± 16 years, P = .05), had more severe thrombocytopenia (platelet count 46,300 ± 30,400/mm³ vs. 62,500 ± 34,400/mm³, P = .02), and developed it earlier (6.0 ± 2.9 vs. 7.4 ± 3.1 days, P = .03). Multivariate analysis showed that severity of thrombocytopenia and early fall in platelet count were independent risk factors for development of thrombotic complications. We did not find an association between development of thrombosis and clinical events (myocardial infarction, cardiac procedures or surgery, noncardiac surgery, and sepsis) that occurred immediately prior to onset of thrombocytopenia. Heparin was stopped in all 32 patients with HITT. Six received no additional therapy, and one received a single dose of aspirin. Three of these 7 died. The other 25 received anticoagulant or multiagent therapy, with 2 deaths. The death rate was lower in those who were treated with anticoagulant or multiagent therapy (P = .05). We conclude that: 1) Thrombotic complications occur in about 29% of hospitalized patients who develop HIT. 2) Early, severe fall in platelet count in elderly patients receiving heparin appears to be associated with development of thrombotic complications. 3) Our data do not show an association between development of thrombotic complications and clinical events immediately preceding the diagnosis of HIT. 4) In addition to discontinuation of heparin, anticoagulant or thrombolytic therapy should be considered in patients with HITT. Am. J. Hematol. 56:12–16, 1997. © 1997 Wiley-Liss, Inc.     

Heparin-induced thrombocytopenia

Thrombocytopenia is a common adverse effect of heparin therapy. Two types of heparin^linduced thrombocytopenia (HIT) are observed clinically - an early onset mild thrombocytopenia (Type I) in which the patients remain asymptomatic and a delayed onset severe thrombocytopenia (Type II). Patients with Type II HIT have an increased risk of thrombotic complications which frequently cause crippling disability e.g. limb amputation or even death. Type I HIT, the commoner of the two types, is believed to be due to the platelet proaggregating effect of heparin itself but Type II HIT is generally agreed to be caused by an immune mechanism, in which heparin-antibody complexes bind to platelets resulting in platelet activation, reduced platelet survival, thrombocytopenia and, in some cases, thrombosis. The diagnosis of HIT is made mainly on a clinical basis but in patients with suspected Type II HIT, laboratory test for the heparin-dependent antibody using platelet aggregometry or the two-point ¹⁴C-serotonin release method, allows confirmation of the diagnosis. In most Type I and all Type II patients, heparin should be stopped and warfarin commenced if there is a recent or new thrombosis requiring continuing anticoagulation. An alternative antithrombotic drug such as low molecular weight heparinoid (Org 10172) or dextran should be given at the same time until warfarin becomes therapeutic. The use of low molecular weight heparins (e.g. Fragmin) should be avoided unless it can be demonstrated that the HIT antibody does not cross-react with these drugs. (Aust NZ J Med 1992; 22: 145–152.)     

The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study

Although heparin-induced thrombocytopenia (HIT) is a known complication of intravenous unfractionated heparin (UFH), its incidence in medical patients treated with subcutaneous UFH is less well defined. To determine the incidence of HIT in this category of patients, the platelet count was performed at baseline and then every 3 +/- 1 days in 598 consecutive patients admitted to 2 medical wards and treated with subcutaneous UFH for prophylactic (n = 360) or therapeutic (n = 238) indications. The diagnosis of HIT was accepted in the case of a platelet drop of 50% or more and either the demonstration of heparin-dependent antibodies or (when this search could not be performed) the combination of the following features: (1) the absence of any other obvious clinical explanation for thrombocytopenia, (2) the occurrence of thrombocytopenia at least 5 days after heparin start, and (3) either the normalization of the platelet count within 10 days after heparin discontinuation or the earlier patient's death due to an unexpected thromboembolic complication. HIT developed in 5 patients (0.8%; 95% CI, 0.1%-1.6%); all of them belonged to the subgroup of patients who received heparin for prophylactic indications. The prevalence of thromboembolic complications in patients with HIT (60%) was remarkably higher than that observed in the remaining 593 patients (3.5%), leading to an odds ratio of 40.8 (95% CI, 5.2-162.8). Although the frequency of HIT in hospitalized medical patients treated with subcutaneous heparin is lower than that observed in other clinical settings, this complication is associated with a similarly high rate of thromboembolic events.     

Heparin-induced thrombocytopenia

BACKGROUND AND OBJECTIVE: There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight and asymptomatic reduction in platelet count, occurring in the first 1-2 days of therapy, that resolves spontaneously; in contrast, HIT II, which has an immunologic origin, is characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withdrawal. HIT II is the most frequent and dangerous side-effect of heparin therapy; in fact, in spite of thrombocytopenia, it can be complicated by venous and arterial thrombosis. Therefore, the recognition of HIT II may be difficult due to the underlying thrombotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical guidelines for the clinical diagnosis and treatment of HIT II. STATE OF THE ART: The prevalence of HIT II, as confirmed by laboratory tests, seems to be about 2% in patients receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The immunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-heparin/ PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-heparin/PF4 immunocomplex activates platelets mainly through binding with the FcgRIIa (CD32) receptor. The onset of thrombocytopenia is independent of the dosage, schedule and route of administration of heparin. Orthopedic and cardiovascular surgery patients receiving post-surgical prophylaxis or treatment for deep venous thrombosis are at higher risk of HIT II. Besides thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses which carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-dependent antibodies. Functional tests, such as platelet aggregation and (14)C-serotonin release assay and immunologic tests, such as the search for anti-PF4/heparin complex antibodies by an ELISA method are available. If HITT II is probable, heparin must be immediately suspended and an alternative anticoagulant therapy should be initiated before resolution of thrombocytopenia and the following treatment with a vitamin K antagonist. The general opinion is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direct thrombin inhibitors such as hirudin. PERSPECTIVES: Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors that induce the occurrence of thrombotic complications. The best therapeutic strategy remains to be confirmed in larger clinical trials.     

Heparin-induced thrombocytopenia: a frequent complication after cardiac surgery

Thrombocytopenia is a common problem in cardiovascular patients, and heparin-induced thrombocytopenia (HIT) is therefore frequently suspected. Unfractionated heparin during cardiopulmonary bypass is particularly immunogenic as 25% to 50% post-cardiac surgery patients develop heparin-dependent antibodies but only 1 to 3% will develop HIT. These antibodies recognize a 'self protein', platelet factor 4 (PF4), bound to heparin. Antibodies associated with a high risk of HIT are mainly IgG1 which strongly activate platelets and coagulation, thereby causing thrombocytopenia and thrombosis. A biphasic evolution of platelet count with a secondary decrease after a previous increase following CPB or non-recovery of thrombocytopenia within 6 days post-operatively always requires screening for HIT antibodies. Both functional (platelet activation tests) and immunologic assays (antigen assays) are necessary in every patient to establish the diagnosis of HIT. When the clinical probability of HIT is high, the first requirement is to discontinue heparin, without waiting for results of laboratory investigations. An alternative anticoagulant such as danaparoid sodium (Orgaran) or lepirudin (Refludan) must then be administered since heparin withdrawal alone is insufficient to control the prothrombotic state associated with HIT. The risk of HIT will probably soon decrease due to the wider use of fondaparinux, which does not interact in vitro with PF4, but it could remain significant in patients undergoing cardiac surgery with CPB.     

Computerised risk scores to guide recognition and diagnosis in patients with possible heparin‐induced thrombocytopenia

The heparin‐induced thrombocytopenia computerised risk (HIT‐CR) score is designed to aid in the diagnosis of HIT. We sought to evaluate its potential clinical utility. In this retrospective cohort study, we collected HIT‐CR scores on all inpatients receiving heparin over a 4‐month period and performed chart reviews on the subset who independently underwent clinical diagnostic testing for HIT to identify patients with HIT. In all, 34 342 patients received heparin, 1744 had high‐risk HIT‐CR scores of ≥3 and 220 had the maximal risk score of 4. Only 6% of high‐risk and 10% of maximal‐risk patients underwent testing for HIT. Conversely, among all 317 patients who underwent independent testing for HIT, 67% had low‐risk HIT‐CR scores (<3). Among patients independently tested, the positive predictive value (PPV) was 6·6% [95% confidence interval (CI) 4·9–8·8%] and the negative predictive value (NPV) was 99·5% (95% CI 97·1–99·9%) at a HIT‐CR score cut‐off of 3, and the PPV was 22·7% (95% CI 12·7–37·4%) and NPV was 99·0% (95% CI 97·6–99·6%) at a cut‐off of 4. This study suggests clinicians fail to test most high‐risk patients and unnecessarily test many low‐risk patients for HIT. A reasonable approach to clinical application of HIT‐CR scores would be recommending no testing for patients with a score of <3 and recommend testing for patients with a score of 4.     

Heparin-induced thrombocytopenia

Summary Heparin-induced thrombocytopenia (HIT), next to bleeding complications, is the most important side-effect of heparin therapy in cardiac patients and the most frequently found thrombocytopenia induced by medication. Two types of HIT are distinguished on the basis of both severity of disease, and pathophysiology: type I HIT is an early, transient, clinically harmless form of thrombocytopenia, due to direct heparin-induced platelet aggregation. Thromboembolic complications are usually not seen. No treatment is required. A normalization of platelet count even if heparin is continued is a usual observation. Type II HIT is more severe than type I HIT and is frequently complicated by extension of preexisting venous thromboembolism or new arterial thrombosis. The thrombocytopenia is caused by a pathogenic heparin-dependent IgG antibody (HIT-IgG) that recognizes as its target antigen a complex consisting of heparin and platelet factor IV. Type II HIT should be suspected when the platelet count falls to less than 100,000 per cubic millimeter or less than 50% of the base line value 5 to 15 days after heparin therapy is begun, or sooner in a patient who received heparin in the recent past. The clinical diagnosis of type II HIT can be confirmed by several sensitive assays. In cases of type II HIT, heparin must be stopped immediately. However, if the patient requires continued anticoagulant therapy for an acute event such as deep venous thrombosis, substitution of an alternative rapid-acting anticoagulant drug is often needed. In the authors experience Danaparoid sodium, a low-sulfated heparinoid with a low cross-reactivity (10%) to heparin, can be regarded as an effective anticoagulant in patients with type II HIT. Preliminary experiences with intravenous recombinant hirudin are also encouraging and suggest that this direct thrombin inhibitor will emerge as a valuable alternative treatment for patients who suffer from HIT.     

Anticoagulant-induced skin necrosis in a patient with hereditary deficiency of protein S

Skin necrosis is a rare but debilitating complication of treatment with vitamin K antagonist anticoagulants such as warfarin. A clinically similar syndrome has been reported less frequently with heparin therapy. We recently managed a thirty-year-old female patient who developed skin necrosis on her left lower extremity while on warfarin for postpartum DVT. The lesions started to develop 48 hr after stopping heparin therapy. Discontinuation of warfarin and reinstitution of heparin was complicated by a rapid decrease in platelet count consistent with heparin-induced thrombocytopenia (HIT) and its associated risk of platelet activation and thrombosis. The diagnosis was supported by the identification of antibodies against heparin/platelet factor 4 complexes in the patient's serum. The platelet count recovered and the patient improved after switching to therapy with the heparinoid danaparoid. Evaluation for a hypercoagulable state revealed a partial deficiency of protein S, a condition that previously was identified in two of her family members. It is not clear if this patient suffered from warfarin-induced skin necrosis, a manifestation of heparin-mediated platelet activation, or a complex condition in which both drugs contributed. HIT may affect 1-3% of patients who receive unfractionated heparin, and this case raises the possibility that heparin may contribute to, or cause, some episodes of skin necrosis attributed to warfarin. Because many patients who develop warfarin-induced skin necrosis have been treated initially with heparin, it would seem prudent to consider HIT in these situations.     

Heparin induced thrombocytopenia

This article describes the pathogenesis, diagnostics, treatment and prevention of heparin induced thrombocytopenia (HIT). Although HIT is considered to be a hematological diagnosis, every physician who treats patients with heparin can encounter it in daily practice. It is even more probable that surgeons of any specialisation will meet with HIT patients. A section of them elude diagnostic detection. There are two forms of HIT - HIT I and HIT II. HIT I is caused by a direct pro-aggregation effect of heparin. It has no clinic significance. HIT II is an antidote mediated adverse reaction to heparin. Antidotes will generate only after the exposure to heparin. They are targeted against the platelet factor 4 and they act only at the presence of heparin. They may lead to the aggregation of thrombocytes in the vascular system (there is a decrease in thrombocyte count). This event can be accompanied by a development of venous or arterial thrombosis that can have a rapid and even fatal course. This fact clarifies the importance of HIT II diagnostics. Diagnosis of HIT II is based on recognizing of the typical decrease in thrombocyte count usually 1 day after heparin administration is initiated. Clinical manifestations are more likely in patients with already damaged endothelium. If thrombocyte count decrease is not connected with clinical manifestations, it is the so called isolated HIT II and in patients who display the signs of thrombosis, it is HIT II associated with thrombosis. The goal of this article is apart from implementing the recommendations of the 7th conference of the American Respiratory Society in real life also the exploration of the diagnostic and therapeutic limits (availability) in the Czech Republic.