Discontinuation Of Heparin Research Articles

Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low‐molecular‐weight heparins: a meta‐analysis

We analyzed the correlation between thrombus regression on control venography performed after discontinuation of heparin therapy and recurrent venous thromboembolism (VTE) detected during clinical follow-up in randomized trials comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in patients with deep vein thrombosis (DVT). Data were abstracted from MEDLINE, conference abstracts and reference lists of previous reviews. Randomized, controlled trials comparing LMWH and UFH for the treatment of DVT using a combined venographic and clinical assessment and with at least 2 months of follow-up were selected. The proportions of patients with thrombus regression on control venography performed soon after discontinuation of heparin therapy and recurrent VTE at 2-6 months were independently collected by two researchers. Thirteen studies met the inclusion criteria. There was a strong inverse correlation between thrombus regression and recurrent VTE (r =- 0.70; P =0.008). The venographic effect varied between the different LMWHs (P = 0.013). A very strong correlation was found when the results were pooled by the type of LMWH used (r = - 0.84; P=0.037). No influence of the dose interval used on the venographic effect (P=0.156) or on recurrent VTE (P=0.218) was shown. The lack of thrombus regression in venography, performed soon after heparin discontinuation, was correlated with clinical recurrence. Non-invasive imaging techniques should be relevant to identify non-responders and to assess the optimal duration of initial heparin treatment in daily clinical practice.

Thrombosis and hemorrhage in heparin-induced thrombocytopenia in seriously ill patients.

Heparin-induced thrombocytopenia (HIT) is the most common form of drug-induced immune-mediated thrombocytopenia. HIT may be aggravated by life-threatening arterial and venous thrombosis and, to a lesser extent, hemorrhagic complications. We investigated the incidence of thromboembolic and hemorrhagic complications in critically ill patients with the multiple organ dysfunction syndrome and HIT. Case-control study. A 33-bed general intensive care unit in a university-affiliated teaching hospital. Twenty consecutive patients with laboratory-proven HIT compared with 20 contemporary, consecutive patients without HIT. Unfractionated heparin or low-molecular-weight heparin were replaced by danaparoid sodium in patients with HIT. Heparin-induced thrombocytopenia was proven by a positive platelet aggregation test. The HIT group consisted of 14 males and 6 females aged 65.2+/-10.8 years (mean +/- standard deviation) with APACHE II scores of 26.7+/-5.4. Thrombocytopenia less than 100 x 10(9)/l developed within 6.4+/-7.0 days. In 12 patients thrombocytopenia resolved after discontinuation of unfractionated heparin in 8.8+/-6.4 days. Arterial and venous thromboembolic complications occurred more frequently in HIT patients than in non-HIT patients (10/20 (50%) versus 0/20 (0%); chi-square p<0.001). Hemorrhagic complications also occurred more frequently in HIT patients than in non-HIT patients (17/20 (85%) versus 7/20 (35%); chi-square p=0.001). In critically ill patients with HIT, the incidence of thromboembolic complications and hemorrhagic complications was remarkably high.

Heparin-induced thrombocytopenia: twenty-nine years later.

To determine the current frequency, types of patients, indications for testing, morbidity and mortality, and management of heparin-induced thrombocytopenia (HIT). Between December 1998 and July 2001, the charts of 102 inpatients that tested positive for heparin-associated antiplatelet antibodies (HAAb) were reviewed. There were 33,941 inpatients, 10,348 of them having received unfractionated or low molecular weight heparins. HAAb were determined by platelet aggregometry. There were 58 males and 44 females with a mean age of 56 years. The majority (72%) of patients were admitted to a surgical service (23% were admitted to medicine, and 5% were admitted to obstetrics/pediatrics). Indications for testing included one or more low platelet counts (n = 51), unexplained arterial (n = 33) or venous (n = 6) thromboses, resistance to anticoagulation (n = 1), prior history of HAAb (n = 3), organ transplant (n = 17), or other indication (n = 4). The HAAb "patterns" were variable, with patients having antibodies only to bovine (n = 7) or porcine heparin (n = 5), bovine and porcine heparins (n = 17), enoxaparin (n = 3), fragmin (n = 7), or all 4 heparins (n = 43). The HIT-related mortality was 6.9%, and the morbidity was 30% with 19 arterial and 7 venous thromboses and 5 bleeding events. Management consisted of discontinuation of heparin in 95 patients. Twenty-five patients did not require continued anticoagulation. When needed, anticoagulation was continued with a direct thrombin inhibitor (n = 32), enoxaparin (n = 16), warfarin (n = 15), or aspirin (n = 7). Seven patients continued to receive unfractionated heparin (n = 4) or low molecular weight heparin (n = 3). HIT occurs in 0.99% of inpatients receiving heparin and remains an important nondiscriminatory contributor to their morbidity and mortality. Patients receiving any form of heparin who develop a decreasing platelet count, unexplained thrombosis, or resistance to heparin anticoagulation should be tested for HAAb. If HAAb are detected, patients must not receive the sensitizing heparin(s).

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

AbstractAlthough 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 Occurring After Discontinuation of Heparin

Heparin-induced thrombocytopenia is caused by antibody formation to heparin-platelet factor 4 complexes. It typically develops 5 to 14 days after the initiation of heparin, but it can occur up to 3 weeks after the patient stops taking it. Early recognition by monitoring platelet counts during heparin therapy can decrease associated mortality and morbidity. A case is described of a patient with severe morbidity as a result of heparin-induced thrombocytopenia. The medical literature was searched using the key words "heparin/adverse effects" and "thrombocytopenia." The severe morbidity and potential mortality associated with heparin-induced thrombocytopenia are caused mainly by thrombosis. If it is suspected, all heparin products should be immediately stopped. Platelet counts usually return to normal after the heparin is discontinued. Approximately 50% of patients with heparin-induced thrombocytopenia develop thrombotic events. Patients should receive anticoagulation with agents other than heparin or low molecular weight heparin. As early detection of heparin-induced thrombocytopenia seems to improve outcome, it is recommended that all patients on heparin should have frequent monitoring of platelet counts.

Current agents for the treatment of patients with heparin-induced thrombocytopenia.

Several counterintuitive treatment paradoxes complicate the management of immune heparin-induced thrombocytopenia (HIT). For example, simple discontinuation of heparin often fails to prevent subsequent HIT-associated thrombosis. Thus, current treatment guidelines recommend substituting heparin with a rapidly acting alternative anticoagulant (eg, danaparoid, lepirudin, or argatroban) even when HIT is suspected on the basis of thrombocytopenia alone ("isolated HIT"). Another paradox-coumarin (warfarin) anticoagulation-can lead to venous limb gangrene in a patient with HIT-associated deep-vein thrombosis. Thus, warfarin is not recommended during acute thrombocytopenia secondary to HIT. However, warfarin can be given as overlapping therapy with an alternative anticoagulant, provided that (1) initiation of warfarin is delayed until substantial platelet count recovery has occurred (to at least above 100 x 10(9)/L); (2) low initial doses of warfarin are used; (3) at least 5 days of overlapping therapy are given; and (4) the alternative agent is maintained until the platelet count has normalized. It has recently been recognized that HIT antibodies are transient and usually do not recur upon subsequent re-exposure to heparin. This leads to a further paradox-patients with previous HIT can be considered for a brief re-exposure to heparin under exceptional circumstances; for example, heart surgery requiring cardiopulmonary bypass, if HIT antibodies are no longer detectable using sensitive assays. For patients with acute or recent HIT who require urgent heart surgery, other approaches include use of alternative anticoagulants (eg, lepirudin or danaparoid) for cardiopulmonary bypass or antiplatelet agents (eg, tirofiban or epoprostenol) to permit intraoperative use of heparin.

Thromboseprophylaxe in der Schwangerschaft nach Polytraumatisierung mit Splenektomie und Immobilisation bei heparininduzierter „relativer“ Thrombozytopenie Typ II

Die heparininduzierte Thrombozytopenie (HIT) wird oft erst beim Auftreten thromboembolischer Komplikationen, seltener durch kutane Intoleranzreaktionen evident [[10]]. Die Häufigkeit einer HIT wird mit etwa 0,5 - 5 % aller mehr als 5 Tage mit Heparin behandelten Patienten angegeben [[8]]. Gefürchtet ist die immunologisch vermittelte HIT vom Typ II die zum „white-clot-syndrome“ führen kann [[4], [9]]. Neben dem Absetzen von Heparin kann bisher nur der Wirkstoff Danaparoid-Natrium (Orgaran® [[11]]), bei der Behandlung schwangerer Patientinnen eingesetzt werden, worüber mehrere Fallberichte existieren [[1], [4]]. Eine Verwendung rekombinanter Hirudine (Lepirudin-Refludan®, Desirudin-Revasc®) ist in der Schwangerschaft bisher nicht zugelassen. Auch bei Labordaten, die eigentlich noch normal sind, muss bei klinischen Verdachtsmomenten ohne Verzögerung die entsprechende Diagnostik und Therapie erfolgen. Da die klinische Erfahrung bei der Behandlung der HIT-Typ II mit Orgaran® sich auf einzelne Fälle beschränkt, wird anhand einer Fallbeschreibung die Möglichkeit der Thromboseprophylaxe mit Orgaran® aufgezeigt.

Thrombopénie induite par l’héparine : présentation d’une observation avec complications thrombotiques graves et revue de la littérature

PURPOSE: Review of the frequency, clinical and biological features and treatment of type II heparin-induced thrombocyopenia. METHODS: Case report and literature review. RESULTS: A 65 years old woman received as antithrombotic prophylaxis low molecular weight heparin (LMWH) after prosthetic knee replacement. Day 8, asymptomatic deep vein thrombosis was discovered after systematic echodoppler examination. Curative anticoagulation was started with LMWH. A fall in the platelet count (17 G/L) was noted day 12. Danaparoid was immediately introduced and heparin discontinued. However, day 16 a massive pulmonary embolism occurred which required transfer to an intensive care unit. Danaparoid was changed for lepirudin the same day. It took longer than three weeks for platelet count to return to normal value after heparin discontinuation. The suspicion of heparin-induced thrombocyopenia was confirmed by specific tests. DISCUSSION: HIT type II are rare but life-threatening and thrombosis events are the most frequent complications. The diagnosis is a high probability proved by both clinical and biological patterns. The treatment consists in alternative thrombin inhibitors such as danaparoid and lepirudin. The platelet count usually requires less than ten days to recover normal values after heparin withdrawal. Cases in which the delay to a normal platelet count exceeds 3 weeks have been reported specially after LMWH therapy. CONCLUSION: Type II HIT are rare but life-threatening events can occur. The platelet count check-up during heparin therapy must be systematic.

Rebound thrombin generation after heparin therapy in unstable angina: A randomized comparison between unfractionated and low-molecular-weight heparin

ObjectivesThis study compared rebound coagulation in patients with acute coronary syndrome patients after discontinuation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). BackgroundUp to a quarter of patients hospitalized for unstable angina experience recurrent ischemia after discontinuation of UFH or LMWH therapy, which may be the result of rebound coagulation activation and subsequent thrombosis. It is unknown whether UFH and LMWH differ in this respect. MethodsWe randomized 71 patients admitted with unstable angina to intravenous UFH or subcutaneous LMWH (dalteparin) and measured plasma markers of coagulation before, during, and after treatment. ResultsA complete series of measurements was obtained in 59 patients. Plasma prothrombin fragment 1+2 (F1+2) levels decreased in both groups during treatment. After loss of therapeutic plasma drug levels, F1+2increased (within 3 h) to a maximum level at 12 to 24 h that was higher than before or during treatment in both groups (p < 0.0001). In both groups, F1+2levels remained higher than pretreatment up to 24 h after discontinuation. Similarly, thrombin-antithrombin (TAT) levels exceeded treatment and pretreatment levels, at a slower rate after dalteparin than after UFH. However, after dalteparin a higher peak value of TAT was observed. ConclusionsRebound coagulation activation occurs within hours after discontinuation of both UFH and dalteparin. With both drugs, thrombin generation is significantly greater after treatment than before or during treatment. A longer duration or weaning of treatment, or continuation with another anticoagulant treatment, may reduce rebound coagulation activation and ischemic events.

Trombocitopenia induzida por heparina

The aim of this paper is to review current information about the clinical manifestations, diagnosis and management of heparin-induced thrombocytopenia. This was achieved by a bibliographic review using Public Medline and consulting Hematology textbooks. From this study we concluded that heparin-induced thrombocytopenia is a common complication of patients exposed to heparin therapy regardless of underlying conditions. Potentially fatal thrombotic complications have been reported. Therefore, if heparin-induced thrombocytopenia is suspected, an adequate approach including early heparin discontinuation is mandatory. Alternative products for heparin include hirudin and danaparoid sodium. Low-molecular-weight heparin is contraindicated.

Compressive Neuropathy of the Brachial Plexus and Long Thoracic Nerve: A Rare Complication of Heparin Anticoagulation

We present a case of a 69-year-old woman who developed brachial plexopathy and long thoracic nerve palsy secondary to compression from a hematoma while receiving heparin therapy for the treatment of a stroke. The patient was treated conservatively with discontinuation of heparin and had complete resolution of her compressive neuropathy. This is the first report of a patient with long thoracic nerve palsy with a brachial plexopathy complicating anticoagulation. We review the literature on hematoma-induced compressive neuropathies and treatment options. Our review concludes by emphasizing the importance of clinical judgment in determining the best therapeutic modality.

This month in J Lab Clin Med: Issue highlights for June 2001

This month in J Lab Clin Med: Issue highlights for June 2001

Neurotrauma &amp; Deep Vein Thrombosis

Neurotrauma &amp; Deep Vein Thrombosis

Thrombocytopenia after isolated limb or hepatic perfusions with melphalan: the risk of heparin-induced thrombocytopenia.

Three cases of heparin-induced thrombocytopenia (HIT) were observed in patients undergoing isolated limb perfusion (ILP) with melphalan. This occurrence prompted the discontinuation of prophylactic postoperative heparin in ILP patients and its avoidance in patients undergoing isolated hepatic perfusion (IHP). The need to reassess these decisions led to a review of thrombocytopenia in both patient populations. Records of all patients treated with ILP or IHP at our institution from July 1992 through November 1996, were reviewed. Nine IHP patients were tested prospectively for heparin-related antibodies using serum samples obtained perioperatively and during the second postoperative week. Thrombocytopenia (< 100,000 platelets/microL) developed postoperatively in 30% of 131 ILP patients and in 77% of 56 IHP patients. No cases of HIT were identified other than the three who had been previously diagnosed. The prevalence of HIT in heparinized ILP patients was 2.8% (3/108). All nine IHP patients developed heparin-related antibodies postoperatively. Because the prevalence of HIT following ILP is in the range observed in other clinical settings, postoperative heparin prophylaxis is an option. However, it probably should be limited to the first week, and daily platelet counts should be reviewed for a pattern of thrombocytopenia consistent with HIT. The prevalence of heparin-related antibodies after IHP is so high that prophylactic heparin should be avoided in this setting.

Antithrombin activity during the period of percutaneous coronary revascularization: Relation to heparin use, thrombotic complications and restenosis

OBJECTIVESThis study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR.BACKGROUNDHeparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity <70% is associated with thrombosis. There is a prothrombotic state after heparin discontinuation that has not been well explained.METHODSAntithrombin activity was sampled at the start and end of PTCR and the next two mornings in 250 consecutive patients. We recorded occurrence of major thrombotic events, defined as 1) major thrombotic complications of PTCR; 2) major in-lab thrombus formation; or 3) subacute occlusion. Discriminant analysis was employed to evaluate the relationship of AT activity to these events. Change in AT activity and its relationship to heparin was evaluated. Evidence of restenosis at six months was obtained.RESULTSThere were 14 major thrombotic events. Antithrombin activity <70% was strongly (p = 0.006) associated with these events. The AT activity fell significantly through the morning after PTCR when 21% of patients had AT activity <70%; AT activity did not normalize until >20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between AT activity and restenosis.CONCLUSIONSLow AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity.

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia with or without thrombosis has been recognized increasingly as a serious complication of heparin use. This article reviews type 11 heparin-induced thrombocytopenia, which is mediated by an antibody that in most cases has specificity for a complex between heparin and platelet factor 4, a secreted platelet cc-granule protein. The antibody-heparin-platelet factor 4 complex can activate platelets and endothelial cells, thereby initiating thrombosis. Clinical thrombosis in this syndrome may be arterial or venous. Treatment of the syndrome requires discontinuation of heparin and institution of an alternative anticoagulant.

Prognostic value of serum hepatocyte growth factor in patients with acute coronary syndromes.

The present study examined whether or not hepatocyte growth factor (HGF), an endothelium-specific growth factor that stimulates regeneration of the endothelium, is increased or has a prognostic significance in patients with acute coronary syndromes. HGF was measured in 106 patients with coronary artery disease (20 stable effort angina, 12 unstable angina without adverse events, 24 unstable angina with adverse events and 50 acute myocardial infarction) on admission and 21 normal volunteers. The measurements in all patients were recorded before administration of heparin, and in acute myocardial infarction patients they were recorded from days 2 to 6 after heparin discontinuation on day 1. HGF levels (ng/ml) were 0.30+/-0.06 for the controls, 0.31+/-0.08 for stable effort angina patients, 0.31+/-0.08 for unstable angina patients without adverse events, 0.40+/-0.20 for unstable angina patients with adverse events and in acute myocardial infarction patients they were 0.45+/-0.18 on day 0, 0.57+/-0.45 on day 2, 0.50+/-0.35 on day 3, 0.48+/-0.32 on day 4, 0.44+/-0.20 on day 5, and 0.38+/-0.14 on day 6. HGF plays a crucial role in the restoration of injured endothelial cells and is a predictor of adverse events in patients with acute coronary syndromes.

Heparin-Induced Thrombocytopenia

Serious limband life-threatening thromboembolic complications may result from immune-mediated, heparin-induced thrombocytopenia (HIT) type II. The authors describe three such cases associated with devastating outcomes. The clinical diagnosis of HIT II was based on (1) falling platelet count on heparin (&lt; 150,000/mm3), (2) thromboembolic events on heparin, and (3) absence of new thrombotic events after heparin discontinuation. These distinct case presentations are discussed to broaden clinical awareness of HIT II. A high index of suspicion is warranted to prevent this catastrophic complication.

Recent advances in the management of unstable angina and non-Q-wave myocardial infarction

Recent advances in the management of unstable angina and non-Q-wave myocardial infarction

Case studies in therapeutics: warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant‐associated priapism

Case studies in therapeutics: warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant‐associated priapism