The emergency use of recombinant hirudin in cardiopulmonary bypass

The most common anticoagulant used for cardiopulmonary bypass is heparin. An alternate form of anticoagulant therapy is needed for patients who have immune-mediated heparin-associated thrombocytopenia (HIT). Thrombocytopenia causes bleeding and may lead to serious arterial and venous thrombosis. HIT or heparin-induced thrombocytopenia with thrombosis type II (HITT) are both described as adverse reactions to heparin. They are diagnosed with a platelet count less than a 100,000/mcl for 2 consecutive days. HITT, the severe form, is characterized with the thrombocytopenia in combination with thromboembolic complications, such as strokes, myocardial infarctions, and limb ischemia. Two cases are presented in which r-hirudin was used for anticoagulation for aortocoronary bypass surgery and mitral valve replacement. The activated partial prothrombin time (aPTT) was used to monitor coagulation. In the first case, the aPTT was maintained greater than 100 seconds, and at the termination of cardiopulmonary bypass, some clot was noted in the cardiopulmonary bypass circuit. In the second case, a longer cardiopulmonary bypass run was anticipated, the hirudin bolus and infusion rate were increased, and the aPTT was maintained at greater than 200 sec. Adequate coagulation resulted, and, at the end of bypass, no clot was noted. These case studies seem to suggest a higher dosage of r-hirudin may be required for the use of cardiopulmonary bypass and a need to maintain aPTT values greater than 200 sec to help monitor anticoagulation.     

Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches

BACKGROUND: Although patients after Fontan procedure have a high incidence of thromboembolic complications, anticoagulant therapy is not handled uniformly. We analyzed the frequency and clinical relevance of thromboembolism after Fontan procedure and compared different therapeutic approaches. METHODS: From 1986 to 1998, 101 patients (mean age, 7.3 +/- 8.1 years) underwent Fontan type procedure (modified Fontan, n = 40; total cavopulmonary connection, n = 61). In 85 of 87 survivors, transthoracic echocardiography was performed; and in 31 transesophageal echocardiography and/or angiography was performed. Mean follow-up was 5.7 +/- 3.5 years. Three groups with different anticoagulant regimen were compared: group I without medication (n = 45), group II with acetylsalicylic acid therapy (n = 14) and group III with Coumadin (n = 26). RESULTS: Thromboembolic events occurred in 13 of 85 patients (15.3%; 3.3 events/100 patient-years). Type of operation as well as other known risk factors had no influence on the rate of thromboembolism. Within the first postoperative year, seven of 13 events occurred. A second peak developed beyond 10 years of follow-up. Patients benefit significantly from Coumadin compared with those who did not receive any medication, with similar results in the entire population and the subgroup of patients with total cavopulmonary connection (log-rank, p = 0.031 and p = 0.033, respectively). With 4.2 events/100 patient-years, the cumulative event rate was substantially higher in group I than with 1.6 in group II and with 1.1 in group III. No relevant bleeding complications occurred. CONCLUSIONS: Thromboembolism is frequent after Fontan procedure with a peak during the first postoperative year and another peak beyond 10 years of follow-up. Coumadin is the most effective prophylactic therapy in preventing thromboembolism. Therefore, we suggest initial oral anticoagulation therapy in patients with Fontan type operation.     

原位肝移植肝动脉重建临床分析

目的 总结分析原位肝移植肝动脉重建经验,提高肝移植疗效和受体存活率.方法 总结1995年5月至2006年12月实施的183例肝移植临床资料,常规动脉重建163例,供者腹腔动脉干Carrell's袖片或肝总动脉-脾动脉汇合部与受者肝左-右动脉汇合部吻合25例,胃十二指肠-肝固有动脉汇合部吻合134例,腹腔动脉干吻合4例.采用髂动脉.腹主动脉搭桥20例.术后根据凝血酶原时间(PT),应用普通肝素或低分子肝素抗凝.术中、术后应用多普勒超声监测肝动脉血供.结果 183例肝移植患者中有6例发生肝动脉并发症,发生率为3.28%(6/183),其中肝动脉血栓形成(hepatic artery thrombosis,HAT)5例,肝动脉狭窄(hepatic artery stenosis,HAS)1例.常规通路动脉重建组动脉并发症发生率1.84%(3/163),髂动脉-腹主动脉搭桥组为15.0%(3/20),两者比较差异有统计学意义(X2=9.73,P＜0.01).6例并发症患者中有1例HAT于术后19 d死于多器官功能衰竭,另5例通过介入治疗治愈,死亡率16.7%.结论 正确地选择肝动脉重建吻合的部位和术后有效的抗凝治疗减少HAT和HAS的发生,多普勒超声的早期发现和放射介入的及时治疗可以挽救移植物,避免再移植.     

Ancrod: a practical alternative to heparin

To rapidly start systemic anticoagulation there are few alternatives to heparin; those that may be used are often less effective and are impractical substitutes for various reasons. We report the cases of seven patients in whom anticoagulant therapy was begun with ancrod instead of heparin for one or more of the following reasons: (1) failure to achieve systemic anticoagulation in response to heparin (e.g., antithrombin III deficiency), (2) heparin-associated complications (e.g., thrombocytopenia, thrombosis, or both), and (3) combined anticoagulation and improved blood rheology considered to be potentially more beneficial than anticoagulation alone (e.g., massive thrombosis). In the cases reported, ancrod permitted systemic anticoagulation equal to that of heparin; this was achieved without bleeding complications. In contrast to streptokinase or urokinase, ancrod does not degrade preformed, fully cross-linked thrombin fibrin; consequently hemorrhagic complications are uncommon. Ancrod appears to be an appropriate alternative to heparin and may be preferable to it in certain circumstances.     

Liver transplantation for Budd-Chiari syndrome: A retrospective study

A retrospective study was performed on 11 patients who underwent orthotopic liver transplantation for Budd-Chiari syndrome (BCS), 3 of whom had fulminant type BCS and 8, chronic type BCS. Both the 3- and 5-year actuarial survival rates were 64%, after one patient with fulminant, and three with chronic disease died of sepsis or multiple organ failure following transplantation. Anticoagulation therapy in the early postoperative period was tailored to each individual patient. Most of the patients received heparin for several days and were then converted to Coumadin therapy, although some were not given heparin in the immediate postoperative period but were instead commenced on oral Coumadin after the prothrombin time had recovered to wihtin the normal range. All the long-term survivors had received Coumadin therapy and there was no recurrence of BCS and no early thrombotic or hemorrhagic event. One patient developed late thrombosis of the portal vein despite having received apparently adequate Coumadin therapy. It was thus concluded that liver transplantation is an effective therapy for both fulminant and chronic BCS, and that immediate postoperative heparinization is not mandatory for all patients.     

The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors

Twenty-three patients with malignant glial neoplasms were treated with anticoagulant therapy for thromboembolic complications. Fifteen patients had deep vein thrombosis alone, and 8 patients had both deep vein thrombosis and pulmonary embolism. Serum prothrombin times were maintained at 1.25 times control for an average of 5.8 months per patient, for a total patient exposure to warfarin therapy of 132 patient-months (11 patient-years). Only 1 patient suffered a recurrent pulmonary embolism, and this occurred during an episode of gastrointestinal bleeding, when anticoagulant therapy had to be discontinued prematurely. All patients were followed with serial computed tomographic or magnetic resonance imaging scans, and no patient showed radiographic evidence of intratumoral hemorrhage either during or after warfarin therapy. One patient, who died from a large recurrent glioblastoma, was found at autopsy to have scattered foci of intratumoral hemorrhage. This series, together with a review of the available literature, suggests that oral anticoagulant therapy is both a safe and effective means of treating thromboembolic complications in patients with residual malignant glial tumors.     

Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival

BACKGROUND: Cardiac xenograft function is lost due to delayed xenograft rejection (DXR) characterized by microvascular thrombosis and myocardial necrosis. The cause of DXR is unknown but may result from thrombosis induced by antibody-mediated activation of endothelial cells and/or by incompatibilities in thromboregulatory interactions. METHODS: To examine these issues, a series (Groups 1-6) of previous transgenic CD46 pig-to-baboon heterotopic cardiac transplants were reanalyzed for baseline immunosuppressive levels, graft survival and infectious complications with and without systemic anticoagulation. Groups 1-4 received low dose tacrolimus and sirolimus maintenance therapy, with splenectomy, anti-CD20 and daily alpha-Gal polymer. Group 1 recipients received no anticoagulation. Groups 2-4 were anticoagulated with aspirin and Plavix, Lovenox, or Coumadin, respectively. Group 5 was treated with Lovenox and high dose tacrolimus and sirolimus maintenance therapy. Group 6 recipients received no postoperative anticoagulation but the same immunosuppression as group 5. RESULTS: Median survival (15-22 days) within groups 1-4 was not significantly different. At rejection all tissues exhibited microvascular thrombosis, coagulative necrosis and similar levels of platelet and fibrin deposition. Groups 5 and 6 median survival (76 days) was significantly increased compared to groups 1-4. There was no significant difference in median survival between Lovenox treated recipients (68 days) and anticoagulant free recipients (96 days). Rejected tissues showed vascular antibody deposition, microvascular thrombosis, and myocyte necrosis. CONCLUSION: Significant prolongation in xenograft survival is achieved by improved immunosuppression. These results suggest that ongoing immune responses remain the major stimulus for DXR.     

Hemorrhagic Shock with Delayed Retroperitoneal Hemorrhage After Deployment of an Inferior Vena Cava Filter: Report of a Case

Although inferior vena cava (IVC) filter placement has demonstrated an excellent therapeutic efficacy in preventing pulmonary embolism, several filter-related complications have been reported. Among them, retroperitoneal hemorrhage due to IVC perforation is one of the most serious complications. We report herein a female patient who underwent TrapEase IVC filter placement with anticoagulation and thrombolytic therapy for treatment of pulmonary embolism, and later demonstrated hemorrhagic shock 5 days after filter placement. The patient's blood pressure stabilized after the anticoagulant therapy was stopped and she received a blood transfusion. We should therefore carefully observe patients after IVC filter placement, particularly those receiving simultaneous anticoagulation therapy.     

Antiphospholipid syndrome; its implication in cardiovascular diseases: a review

Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.     

Hemorrhagic and Thromboembolic Complications after Bariatric Surgery in Patients Receiving Chronic Anticoagulation Therapy

Background Perioperative management of bariatric surgical patients receiving chronic anticoagulation requires an understanding of potential hemorrhagic and thromboembolic risks. The aim of this study is to evaluate hemorrhagic and thromboembolic complications in morbidly obese patients who are on oral anticoagulation treatment and subsequently undergo laparoscopic bariatric surgery. Methods The medical records of all laparoscopic Roux-en-Y gastric bypass (LRYGB) patients from June 2001 to March 2006 were retrospectively reviewed. In addition, data of patients who received chronic anticoagulation therapy with Coumadin and underwent laparoscopic Roux-en-Y gastric bypass was analyzed. Clinical parameters included length of hospitalization, hemorrhagic complications, thromboembolic complications, conversion rate, reoperation, and blood transfusion. Results During the study period, 1,700 consecutive patients underwent bariatric surgery for the treatment of morbid obesity. Of these, 21 patients were treated with chronic oral anticoagulation; 3 of the 21 (14%) had hemorrhagic complications: one patient had intraluminal hemorrhage and two patients had intraabdominal hemorrhage. Two patients required blood transfusion, and one patient underwent surgical reintervention. None of the 21 laparoscopic operations were converted to open procedures. There were no postoperative mortalities, and there were no thromboembolic events in this series. Conclusions Laparoscopic bariatric surgery can be performed relatively safely in morbidly obese patients who are treated with chronic oral anticoagulation. Even in the presence of bleeding, patients can be successfully treated without the need for reoperation.     

Anticoagulation with enoxaparin versus intravenous unfractionated heparin in postoperative vascular surgery patients

BACKGROUND: The use of postoperative anticoagulation is not uncommon for patients undergoing vascular procedures, whether for adjunctive therapy to the surgical procedure or for resumption of preoperative anticoagulation. We investigated whether low-molecular-weight heparin, specifically enoxaparin, was an effective replacement for intravenous heparin during the postoperative period until achievement of a therapeutic international normalized ratio, together with the impact on postoperative length of stay. METHODS: We retrospectively examined 330 patients who received either traditional intravenous unfractionated heparin with adjusted-dose warfarin daily (n = 169) or subcutaneous low-molecular-weight heparin, specifically enoxaparin 1 mg/kg every 12 hours, with adjusted-dose warfarin daily (n = 161). Safety was defined as incidence of bleeding, hematoma, stroke, expiration, thrombocytopenia, return to surgery for graft thrombosis or hematoma, and readmission within 30 days for hematoma or thrombosis. RESULTS: For all procedures, regardless of type of anticoagulation treatment, there was no difference in the incidence of postoperative complications, except for the increased incidence of return to surgery for graft thrombosis (P =.02), failing graft (P =.0004), and debridement (P =.01) in patients who received unfractionated heparin. For all procedures combined, the average postoperative length of stay was shortened by 2 days with use of low-molecular-weight heparin (P =.0001). CONCLUSIONS: In this series, use of enoxaparin appears to be safe and effective for vascular postoperative anticoagulation. At the same time, its use can significantly reduce the average postoperative length of stay for patients undergoing vascular procedures. Further prospective data are needed before this protocol can be accepted as an alternative for postoperative anticoagulation in this set of patients.     

原位肝移植肝动脉并发症的预防和治疗

目的 总结分析原位肝移植肝动脉重建及其并发症的防治经验,提高肝移植疗效和受体存活率。方法 总结1995年5月至2005年4月实施的122例肝移植临床资料,肝动脉重建采用供者腹腔动脉干Carrell’s袖片或肝总动脉-脾动脉汇合部与受者肝左-右动脉汇合部袖片吻合21（16．76％）,与受者胃十二指肠-肝固有动脉汇合部吻合87例（71．76％）,采用髂动脉-腹主动脉搭桥14例（11．48％）。术后根据凝血酶原时间（PT）,应用普通肝素或低分子肝素预防性抗凝。术中、术后应用多普勒超声监测肝动脉血供。结果 术后肝动脉血栓形成（HAT）3例,肝动脉狭窄（HAS）2例。1例HAT于术后19d死于多器官功能衰竭,另4例通过放射介入治疗治愈。其余病例随访2～62个月,未见肝动脉血栓形成（HAT）和肝动脉狭窄（HAS）。本组肝动脉并发症发生率为4．10％。结论 正确地选择肝动脉重建吻合的部位和术后有效的抗凝治疗可减少HAT和HAS的发生,多普勒超声监测能早期发现HAT和HAS,挽救移植物,避免再移植。     

Hypercoagulable states and antithrombotic strategies in recurrent vascular access site thrombosis

Vascular access site thrombosis is a major cause of morbidity in patients receiving hemodialysis. The role of hypercoagulable states in recurrent vascular access site thrombosis remains poorly understood. Data are limited regarding systemic anticoagulation to improve access graft patency, because of concern about hemorrhagic complications. We determined the prevalence of hypercoagulable states and clinical outcome (thrombotic and hemorrhagic) after initiation of antithrombotic therapy in a series of patients with recurrent vascular access site thrombosis. We evaluated 31 patients who had sustained 119 thrombotic events that resulted in vascular access graft failure during the year before evaluation. Sixty-eight percent of patients tested had elevated concentrations of antibody to anticardiolipin or topical bovine thrombin, and 18% of patients tested had heparin-induced antibodies. More than 90% of patients had elevated factor VIII concentration, 62% had elevated fibrinogen concentrations, and 42% had elevated C-reactive protein concentrations. Twenty-nine patients were given antithrombotic therapy: 13 with warfarin sodium, 12 with unfractionated heparin (UFH), and 11 with low molecular weight heparin (LMWH). Seven patients received more than one antithrombotic agent, sequentially. Nineteen patients have had no thrombotic events since beginning antithrombotic therapy (10 with warfarin, 3 with UFH, 6 with LMWH). Mean follow-up was 8.6 months (median, 7 months). Eight patients sustained 10 bleeding complications (5 with warfarin, 3 with UFH, and 2 with LMWH). In conclusion, hypercoagulable states are common in patients with recurrent vascular access site thrombosis. Antithrombotic therapy may increase vascular access graft patency, but is associated with significant risk for hemorrhage. Prospective studies are needed to evaluate the role and safety of antithrombotic agents in improving vascular access graft patency.     

Extensive experience with dural sinus thrombosis

OBJECTIVE: Dural sinus thrombosis (DST) is an uncommon cause of stroke. The safest and most effective therapy for DST has not been conclusively identified. METHODS: A retrospective chart review of data for 31 patients who were treated for DST at our institution between 1992 and 2001 was performed. Four treatment strategies were identified, i.e., 1). medical observation only, 2). systemic anticoagulation (AC) therapy with heparin, 3). endovascular chemical thrombolysis with urokinase or tissue plasminogen activator and concurrent systemic AC therapy, and 4). mechanical endovascular clot thrombolysis with concurrent systemic AC therapy. Complications and clinical outcomes were assessed for each group. RESULTS: Patients treated solely with medical observation fared the worst; four of five patients experienced intracranial hemorrhagic complications, and only two of five exhibited clinical improvement. Patients who received systemic AC therapy experienced no hemorrhagic complications, even when pretreatment hemorrhage was present; 75% (six of eight patients) exhibited improvement with AC therapy alone. Chemical thrombolysis was very effective in restoring sinus patency (90% of patients); however, 30% of patients (3 of 10 patients) experienced hemorrhagic complications. Sixty percent of patients (6 of 10 patients) who underwent chemical thrombolysis exhibited clinical improvement. Patients who underwent mechanical thrombectomies demonstrated a low hemorrhagic complication rate, and most (88%) made good recoveries. CONCLUSION: Therapy directed at the underlying clot in DST must begin without delay. Our results suggest that supportive medical management of DST, without therapy directed at the clot or clotting process, is not effective. Systemic AC therapy, even in the presence of intracerebral hemorrhage, seems to be safe. Heparin can be safely titrated to yield partial thromboplastin times of 60 to 70 seconds. Chemical clot thrombolysis is efficacious in opening occluded sinuses but may cause intracranial hemorrhage. We currently recommend either systemic AC therapy or systemic AC therapy in conjunction with mechanical clot thrombectomy as a safe effective treatment for DST.     

Arterial thrombosis and embolism in malignancy

In most reviews of arterial embolism or thrombosis the source of emboli or the cause of thrombosis can reasonably be established in over 90% of patients. Still about 10% remain without demonstrable cardiac or intraarterial sources. Although hypercoagulability induced by malignancy has been alluded to as a cause of unexplained intravascular thrombosis reports of arterial thromboembolism with such association are rare. Seven patients with unequivocal thromboembolism are presented. Two distinct clinical patterns are observed, one with in situ thrombosis of small arteries and the other with occlusion of large arteries causing limb ischemia or fatal organ infarction. The various pathogenetic mechanisms of arterial thrombosis or embolism in malignancy include sustained spasm of arteries, precipitation of cryoglobulins or other abnormal proteins in small arteries, direct tumor invasion of arteries, fragmentation and embolization of intracardiac or intraarterial metastases and spontaneous arterial thrombosis due to hypercoagulability. The hypercoagulable state can be recognized by the observation of shortened bleeding and clotting times, partial thromboplastin and prothrombin times, elevation of coagulation factors, platelets and yield stress index and resistance to anticoagulation. Patients presenting with arterial thromboembolic events with out demonstrable source should be investigated for malignancy. Conversely patients with malignancy should be searched for evidence of hypercoagulability in an attempt to prevent arterial thromboembolic complications.     

Prothrombotic states that predispose to stroke

Opinion statement Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparininduced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.     

心脏机械瓣膜置换术后抗凝治疗

抗凝治疗中的出血与栓塞是心脏机械瓣膜置换术后最重要的远期并发症.我国心脏机械瓣膜置换术后患者抗凝治疗的主要矛盾是出血,应降低抗凝强度,减少出血并发症.近年来,心脏机械瓣膜置换术后抗凝治疗的主要进展是采用国际标准比值(INR)监测抗凝和低强度抗凝治疗.目前国内采用的INR为1.5～2.0,凝血酶原时间比值(PTR)为1.3～1.5的抗凝治疗强度,有利于降低抗凝患者的出血病死率以及妊娠妇女、新生儿的并发症,并能改善患者的生活质量.     

Laparoscopic cholecystectomy in anticoagulated patients

Summary Although minimally surgically invasive, laparoscopic surgery has yet to be proven safe in patients receiving anticoagulants. Retrospectively, the laparoscopic management of four patients requiring anticoagulation for cardiac valvular prostheses or chronic atrial fibrillation was reviewed with regard to potential hemorrhagic complications. Warfarin was discontinued preoperatively in all cases. Heparin anticoagulation was individualized according to each patient’s risk for thrombosis. Laparoscopic cholecystectomy and intraoperative cholangiography were completed in each patient without resulting hemorrhagic complications. The operative management of patients exhibiting cholecystitis may be complicated by anticoagulation therapy required for preexisting conditions/diseases such as cardiac valve prostheses, chronic atrial fibrillation, deep venous thrombosis, and pulmonary embolism. The minimally invasive nature of laparoscopic surgery lends itself well to cholecystectomy required in the face of anticoagulation treatment. This limited initial series of selected patients demonstrates the feasibility and efficacy of laparoscopic cholecystectomy in patients receiving anticoagulants.     

Lepirudin is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies.

OBJECTIVE: The purpose of this study was to determine whether lepirudin, a direct thrombin inhibitor, is a safe and effective anticoagulant for patients with heparin-associated antiplatelet antibodies (HAAbs). METHODS: The charts of HAAb-positive patients who received lepirudin were reviewed. Lepirudin use was analyzed for indication, duration, and effectiveness of anticoagulation, and for adverse events. HAAb presence was determined by platelet aggregation. RESULTS: Eighteen HAAb-positive patients received lepirudin: 9 had previous documentation of HAAb, 6 had thrombocytopenia while receiving heparin; and 3 had HAAb after a thrombotic event. The indications for lepirudin anticoagulation included thromboembolism prophylaxis (5), arterial thromboses (5), pulmonary embolus (3) or deep venous thrombosis (1), and one each for atrial fibrillation, myocardial infarction, artificial heart valves, and hemodialysis access. The average duration of therapy was 4.04 days. Fifteen patients achieved adequate anticoagulation (activated partial thromboplastin time [aPTT] ratio > 2.0) with lepirudin. Seven patients had aPTTs that were sometimes supratherapeutic (aPTT > 100 seconds) but did not bleed. In all patients who had heparin-induced thrombocytopenia, platelet counts were normalized while they received lepirudin. There were two complications: one patient fell and had a calf hematoma (aPTT ratio 3.24), and one patient who received lepirudin during nine separate hospitalizations had epistaxis (aPTT ratio 2.86) during her ninth hospitalization. Another patient received lepirudin during two hospitalizations without an adverse event. CONCLUSION: Lepirudin is a safe and effective anticoagulant for patients with HAAbs. The platelet counts of all patients with heparin-induced thrombocytopenia were normalized while they received lepirudin. Careful monitoring of the aPTT and avoidance of trauma while patients are receiving lepirudin are recommended.     

Heparin-associated thrombocytopenia and thrombosis: optimal therapy with ancrod

Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequent occurrence but may have disastrous consequences. Continued therapy with heparin must be avoided and anticoagulation achieved by alternative means. Among the few alternatives to heparin in critically ill patients, the best is ancrod. Depletion of fibrinogen with ancrod results in anticoagulation comparable to therapy with heparin within 12 hours. In a small series, nine patients with HATT were treated with ancrod; one underwent angiographic assessment, angioplasty and subsequent vascular reconstruction. Ancrod therapy was not associated with bleeding complications. It appears to provide optimal therapy for patients suspected of having HATT.