Heparin-Induced Thrombocytopenia from Venous Thromboembolism Treatment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 908-908
Author(s):  
Susan M. Begelman ◽  
Marcie J. Hursting ◽  
Richard V. Aghababian ◽  
David McCollum

Abstract Heparin therapy for any indication, including venous thromboembolism (VTE), can be complicated by heparin-induced thrombocytopenia (HIT). The purpose of this retrospective study was to characterize the clinical experience of patients in whom HIT complicated heparin therapy for VTE and who were switched to argatroban therapy. From the previously reported prospective, multicenter, historical-controlled Argatroban-911 and Argatroban-915 studies of argatroban therapy in HIT, we identified all patients who developed HIT while on heparin therapy for pulmonary embolism and/or deep venous thrombosis and in whom heparin was discontinued and argatroban therapy initiated. The primary study end point was a composite of death, amputation, or new thrombosis within 37 days of argatroban initiation; we also evaluated a 37-day composite end point of thrombosis-associated events, including death due to thrombosis, amputation secondary to HIT, or new thrombosis. A total of 145 patients with VTE and HIT were included in our analysis. During heparin therapy before HIT was diagnosed, platelet counts decreased from daily mean values greater than 175x109/L to a mean±SD nadir of 78±67x109/L over the course of 5 days, and new thrombosis developed in 75 (52%) patients. After heparin was discontinued, patients received argatroban (mean dose 2.1±1.2 mcg/kg/min) for 6.8±4.3 days achieving mean activated partial thromboplastin times during therapy of 63±12 s. By day 6 of argatroban therapy, the mean platelet count had risen to >150x109/L. The primary end point occurred in 41 (28.3%) patients, and the thrombotic composite in 23 (15.9%) patients (Table 1). Seventeen (11.7%) patients, including 12 who had also experienced thrombosis while on heparin, developed new thrombosis after argatroban initiation, typically on the day argatroban was discontinued or later (n=10). Death due to thrombosis occurred in only 1 (0.7%) patient. Seven (4.8%) patients experienced major bleeding. We conclude that in heparin-treated patients with VTE, HIT-associated thrombosis often occurs before HIT is recognized, emphasizing the importance of platelet count monitoring and a high degree of suspicion for HIT in this setting. For VTE patients with HIT, argatroban provides effective anticoagulation, with outcomes comparable with those reported for argatroban-treated patients in whom HIT developed following heparin therapy for any indication. New thrombosis occurring after switching to argatroban therapy more typically occurs in patients with existing HIT-associated thrombosis and at/after argatroban discontinuation. Clinical Outcomes n(%) Outcome n=145 Primary (all cause)* Thrombosis-related†,¥ *All-cause death, all-cause amputation, or new thrombosis within 37 days. †Death due to thrombosis, amputation secondary to HIT, or new thrombosis within 37 days. ¥More than 1 outcome may have occurred in a single patient. Composite end point 41 (28.3) 23 (15.9) Individual components Death 19 (13.1) 1 (0.7) Amputation 8 (5.5) 6 (4.1) New thrombosis 17 (11.7) 17 (11.7)

1993 ◽  
Vol 69 (04) ◽  
pp. 344-350 ◽  
Author(s):  
B H Chong ◽  
J Burgess ◽  
F Ismail

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.


2017 ◽  
Vol 24 (6) ◽  
pp. 944-949 ◽  
Author(s):  
Shinya Motohashi ◽  
Takefumi Matsuo ◽  
Hidenori Inoue ◽  
Makoto Kaneko ◽  
Shunya Shindo

Heparin-induced thrombocytopenia (HIT) is one of the serious complications in patients who undergo cardiac surgery. However, there remains a major problem in diagnosing HIT because the current immunological assays for detection of HIT antibody have limitations. Furthermore, the clinical course of thrombocytopenia in this surgery makes it increasingly difficult to diagnose HIT. We investigated the relationship between platelet count and HIT antibody in 59 patients who underwent cardiac surgery using cardiopulmonary bypass (CPB). The number of postoperative HIT antibody-positive patients evaluated using enzyme-linked immunosorbent assay kit (polyanion IgG/IgA/IgM complex antibodies/antiplatelet factor 4 enhanced) was 37 (62.7%). In contrast, platelet activation by HIT antibody was evaluated using the serotonin release assay (SRA). More than 20% and 50% release of serotonin was obtained from 12 patients (20.3%) and 8 patients (13.6%), respectively. The levels of d-dimer were significantly different on postoperative day 14 between SRA-positive and SRA-negative groups; however, postoperative thrombus complication was not detected using sonography in the patients with positive serotonin release at all. After being decreased by the operation, their platelet count recovered within 2 weeks in both groups equally. In our study, although the patients were positive in the platelet activating HIT antibody assay, they remained free from thrombosis and their platelet count recovered after early postoperative platelet decrease. Therefore, in addition to the SRA, monitoring of platelet count might be still considered an indispensable factor to facilitate the prediction of HIT thrombosis prior to manifestation in the patients undergoing cardiac surgery using CPB.


Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.


2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S80-S80
Author(s):  
Constance Nwadike ◽  
Amarachi Nwakamma ◽  
Harrison Nwanjo ◽  
Denis Nwosu ◽  
Roy Ezekwe

Abstract Objectives The evidence supporting the role of circulating markers of inflammation in the pathogenesis of atria fibrillation remains controversial. This study investigated the levels of serum lipids, C-reactive proteins, erythrocyte sedimentation rate, prothrombin time, and platelet count in subjects with new-onset atria fibrillation (NAF), but with no established cardiac disease, in a Nigerian community. Methods The case control study involved a total of 200 subjects: 110 subjects with NAF and 90 apparently healthy subjects without AF, as control. AF was confirmed by a 12-lead electrocardiogram (ECG), while excluding subjects with high risk. Blood samples from the subjects were analyzed for the following parameters: C-reactive proteins using ELISA method and serum lipids using an enzymatic, colorimetric method; erythrocyte sedimentation rate, by Westergreen method; platelet count using a Midray hematology auto analyzer; and the prothrombin time using a tissue thromboplastin method. Data collected from the result were analyzed using SPSS version 15. Results There was a significant increase in the levels of C-reactive proteins and ESR in subjects with NAF when compared with the control subjects. A significant increase was observed in the mean values of total cholesterol and low-density lipoproteins in subjects with NAF, while that of high-density lipoproteins was lower in NAF than in controls. There was no significant difference in the mean values of triglyceride in NAF and the control. Results also showed significantly reduced prothrombin time, with more platelet count in subjects with NAF. The result demonstrated that females (56.3%) had greater risk of developing AF than males (45.8%), while incidence of AF was observed to increase with age. Conclusion The results of the markers assayed suggest marked dyslipidemia, inflammation, and thrombogenesis in subjects with new-onset AF. Hence dyslipidemia and inflammation play critical roles in the pathogenesis of atria fibrillation.


Author(s):  
Vickie McDonald ◽  
Marie Scully

Coagulation is best thought of using the cell-based model of coagulation. Patients commenced on heparin therapy should have their platelet count monitored early because of the risk of heparin-induced thrombocytopenia, which can occur on any type or dose of heparin. Emergency reversal of warfarin should be with prothrombin complex concentrate (containing factors II, VII, IX, and X) and not fresh frozen plasma. New oral anticoagulants have the advantage of predictable pharmacokinetics and do not require routine monitoring, but optimal reversal strategies for these agents are not clear. Thrombolytic agents lead to variable degrees of systemic lysis, which may cause haemorrhage, including intracerebral haemorrhage


2019 ◽  
Vol 37 (31) ◽  
pp. 2892-2898 ◽  
Author(s):  
Gerald A. Soff ◽  
Yimei Miao ◽  
Gemma Bendheim ◽  
Jeanette Batista ◽  
Jodi V. Mones ◽  
...  

PURPOSE Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment. METHODS We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/μL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/μL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point. RESULTS The mean platelet count at enrollment was 62,000/μL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/μL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/μL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT. CONCLUSION This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.


1936 ◽  
Vol 64 (3) ◽  
pp. 439-452 ◽  
Author(s):  
Robert F. Parker ◽  
Thomas M. Rivers

Methods have been described by which the number of elementary bodies present in a suspension can be estimated. It has been shown that by means of replicate counts, in which the Petroff-Hausser chamber was used, a high degree of accuracy can be attained. By means of the Gates densitometer, the number of elementary bodies in a suspension can be determined with a coefficient of variation of about 3.0 per cent. A method has been described by which the accuracy of estimation of the infectious titer of a suspension can be increased without greatly enlarging the number of animals employed. This consists of selecting as the end-point that dilution of virus which on intradermal inoculation in a rabbit would lead theoretically to an equal number of positive and negative results. The statistical advantages of this method have been confirmed by the experiences of other laboratories. By the application of the methods described, there was shown to be a direct correlation between the number of elementary bodies and the number of infectious units of virus present in a given suspension. At the mean of the distribution this ratio is as the logarithms 9.62 to 8.0. To extrapolate this curve, in order to determine the number of elementary bodies present in a single infectious unit, while tempting, is probably not justifiable. It must likewise be remembered that the data given apply to a particular strain of vaccine virus, and that the number of infectious units has been determined by intradermal inoculation of rabbits. It appears also that this method may be of value in studies of the virulence of different strains of vaccine virus, since by its application one may determine not only the infectious liter of a suspension, but its content of elementary bodies. In the agglutination reaction it was found that optimum titers of serum were obtained when the test antigen contained from 2.0 x 109 to 1.05 x 1010 elementary bodies per cc. Approximately 1.95 x 108 particles per cc. of suspension were required for the production of visible agglutination.


2017 ◽  
Vol 86 ◽  
Author(s):  
Blanka Mahne ◽  
Mladen Gasparini ◽  
Matija Kozak

Background: Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder following heparin therapy presenting with thrombocytopenia and associated arterial or/and venous thrombosis (heparin induced thrombocytopenia with thrombosis–HITT). Unrecognised HIT can lead to severe complications like limb amputation and death.Case report: We report a case of a patient who presented with HIT-associated recurrent lower limb arterial thrombotic occlusions and popliteal venous thrombosis 29 days after coronary bypass graf surgery. The patient underwent urgent thrombectomy of superfcial femoral, popliteal and posterior tibial artery. Because of recurrent thrombotic occlusions of lower limb arteries three surgical revisions were performed. Te platelet count decreased from 124 × 109/l to 53 × 109/l on the fifth day after the first intervention. After clinical suspicion of HIT, heparin was discontinued and fondaparinux was started. Arterial thrombosis did not recur and the patient recovered without consequences.Conclusions: HIT occurs in 1–3 % of patients after cardiac surgery. Strict following of international guidelines regarding the frequency of platelet count monitoring, assessing probability for HIT and laboratory testing is mandatory in order not to miss the diagnosis of HIT. HIT can manifest clinically several days after the first exposure to heparin. If a patient presents with acute thrombosis and thrombocytopenia, HITT should be suspected. Postoperative HIT is associated with higher morbidity and mortality. Early recognition is crucial to prevent severe complications and death.


1981 ◽  
Author(s):  
J A Caprini ◽  
A J Sholder ◽  
J P Vagher ◽  
J Mitchell

Review of 6,000 patient records from our laboratory showed 609 individuals who received continuous intravenous infusion heparin therapy for thromboembolic disease. 40/609 (6.5%) of these patients were found to have a platelet count of less than 150,000 cell/mm . Of this group, 34/40 (85%) exhibited thrombocytopenia prior to heparin therapy that was attributable to consumptive coagulopathy in 21/40 (52.5%), sepsis or malignancy in 11/40 (27.5%), and cimetidine or sulfisoxazole in 2/40 (5%). Heparin therapy had no adverse effect on the platelet count in these individuals, and the count returned to normal in surviving individuals if the underlying cause was successfully treated or the offending drug removed.Only 6/40 (15%) of the patients developed low platelet counts during the course of heparin therapy; this represents 6/609 (0.98%) of the population receiving heparin. The etiology of thrombocytopenia in 5/6 (83%) of the cases was traced to metastatic cancer (3), burn wound sepsis (1), and septic shock (1). Only 1/609 (0.16%) of these patients developed low platelet count that could be attributed to heparin. Thus, the incidence of heparin-induced thrombocytopenia is extremely rare in our hospital population.


2020 ◽  
Vol 8 ◽  
pp. 232470962094409 ◽  
Author(s):  
Prasanth Lingamaneni ◽  
Sriram Gonakoti ◽  
Krishna Moturi ◽  
Ishaan Vohra ◽  
Maryam Zia

COVID-19 (coronavirus disease-2019) infection is a highly prothrombotic state, resulting from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is strongly recommended in these patients, with some experts even advocating for therapeutic dosing to prevent thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. In this article, we report a case of HIT in a patient with COVID-19. A 63-year-old male presented with 1 week of dry cough and diarrhea. He had a positive nasopharyngeal COVID-19 reverse-transcriptase–polymerase chain reaction. On admission, the platelet count and liver function tests were within normal limits. During his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulation. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days 11 and 12 of hospitalization, platelet count dropped from 304 000 to 96 000 cells/µL. He had a high pretest probability for HIT with a 4T score of 6 and a positive anti-PF4/heparin antibody. Heparin drip was discontinued and was switched to argatroban. The serotonin release assay eventually returned positive, which confirmed the diagnosis of HIT. We also discuss potential overdiagnosis of HIT in COVID-19 through 4 cases with false-positive HIT antibodies.


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