scholarly journals Heparin-induced thrombocytopenia type II: Innovations in diagnostics and treatment

2003 ◽  
Vol 56 (5-6) ◽  
pp. 247-250 ◽  
Author(s):  
Nebojsa Antonijevic ◽  
Milica Stanojevic ◽  
Rajko Milosevic ◽  
Danijela Mikovic ◽  
Mirjana Kovac ◽  
...  

Heparin-induced thrombocytopenia (HIT) Management of heparin-induced thrombocytopenia (HIT) and treatment options have significantly changed recently. Heparin may induce two types of thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%), is characterized by mild thrombocytopenia without significant clinical manifestations. Type II is less frequent (0.5-2%), life threatening immune type, develops following a period of minimum 5-7 days upon introduction of heparin therapy (patients earlier treated with heparin are excluded). Type II heparin-induced thrombocytopenia with severely reduced platelet count may be clinically manifested by thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable Sensitivity of a highly specific platelet aggregation assay is only 36% sensitivity and specificity of 14C-serotonin release assays amounts to 95% while ELISA using a heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and antigen assays. Furthermore, new classes of antigen assays, like antibody detection tests of complexes between heparin and neutrophil-activating peptide-2 as well as those between heparin and interleukin-8, have been used. Current therapy options Current therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80?100%. Danaparoid sodium exhibits in vitro cross-reactivity of 10?61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment: lepirudin, especially in patients without renal failure and argatroban, particularly in patients with renal failure. The following procedures and agents are also efficient: asmapheresis in the first four days, high-dose intravenous gammaglobulin, antiagregans, especially ADP antagonists, aspirin, dipirydamole, dextran, prostacyclin analogues thrombolytic therapy as well as thromboembolectomy. Oral anticoagulants are not administered in active HIT type II, in deep vein thrombosis with high international normalized ratio (INR) and thrombin-antithrombin complexes, and low protein C levels to avoid the possibility of venous limb gangrene development. They can be administered in a stable phase, when the thrombin generation is controlled by previous administration of one of the above-mentioned alternative anticoagulants.

1998 ◽  
Vol 32 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Aditya K Gupta ◽  
Michael J Kovacs ◽  
Daniel N Sauder

OBJECTIVE To highlight the importance of heparin-induced thrombocytopenia (HIT), a potentially fatal adverse effect of heparin therapy. CASE SUMMARY: There are two types of HIT with a distinct etiology. Type 1 HIT is a relatively mild thrombocytopenia of early onset that generally resolves with ongoing heparin therapy. Clinical complications are uncommon. Type 2 HIT, which is more severe, is the main focus of this report. Five patients receiving heparin therapy developed type 2 HIT, which in some cases resulted in complications that required limb amputation, or eventuated in death. DISCUSSION: In a patient receiving heparin therapy, the development of thrombocytopenia should alert the caregiver to the possible development of HIT. Prompt management of HIT can help prevent complications. HIT usually manifests 5–8 days after starting heparin therapy. The platelet count usually decreases to less than 100 times 103/mm3. It generally normalizes within 5–7 days after discontinuing heparin therapy. In spite of the thrombocytopenia, thrombosis or disseminated intravascular coagulation can occur. The management may be subdivided into three clinical situations: mild-to-moderate asymptomatic thrombocytopenia, severe thrombocytopenia with a platelet count of less than 50 times 103/mm3, and thrombosis or embolism complicating HIT. CONCLUSIONS Heparin-induced thrombocytopenia is an uncommon but potentially serious, and sometimes lethal, complication of heparin therapy. Therefore, it is important to be aware of the possibility of the development of HIT with heparin therapy, to recognize it early, and to manage it appropriately before the manifestation of adverse effects. OBJETIVO Establecer la importancia de la trombocitopenia inducido por heparina (TIH), lo cual representa un posible efecto adverso fatal associado con la terapia de este medicamento. RESUMEN DEL CASO Existen dos tipos de TIH con etiologias distintas. TIH del tipo I representa trombocitopenia que es relativamente leve y de occurrencia temprana y que se resuelve generalmente con la terapia continua de heparina. Complicaciones clínicas son infrequentes. TIH del tipo II es más severa y representa el foco principal de este reporte. Se describe cinco pacientes que recibieron terapia con heparina que desarrollaron TIH del tipo II y cuyos casos resultaron en complicaciones que necesitaron amputaciones en las extremidades o que aveces resultaron en condiciones fatales. DISCUSSIÓN En pacientes que reciben terapia con heparina, el desarrollo de trombocitopenia debe alertar el médico al posible desarrollo de TIH. El manejo inmediato de TIH puede prevenir estas complicaciones. Después de la primera exposición a la heparina, TIH se manifiesta 5–8 días después del inicio del tratamiento. En estos casos, el número de plaquetas usualmente se disminuye a menos de 100 times 103/mm3 y generalmente se normalisa dentro de 5–7 días al descontinuarse la heparina. A pesar de la trombocitopenia, trombosis y coagulación intravascular deseminada puede desarrollarse en estos pacientes. El manejo de éstas complicaciones puede ser subdividido en tres situaciones clínicas: trombocitopenia asintomático leve o moderada, trombocitopenia severa con un conteo de plaquetas de menos de 50 times 103/mm3 o complicaciones de trombosis y embolismo debido al TIH. CONCLUSIONES TIH es una complicación infrequente, pero este puede resultar en complicaciones serias y a veces letales debido a la terapia de heparina. Como resultado, es importante estar al tanto del posible desarrollo de TIH asociado con el tratamiento de heparina, reconocer esta complicación lo más pronto posible, y manejarlo apropriadamente antes de las manifestaciones de los efectos adversos. OBJECTIF Souligner l'importance de la thrombocytopénie induite par l'héparine (TIH), un effet indésirable potentiellement fatal de l'héparine. RÉSUMÉ DU CAS Il existe deux types de TIH, présentant des étiologies distinctes. Le type I se définit comme une thrombocytopénie légère, d'apparition précoce et qui se résout généralement malgré la poursuite du traitement à l'héparine. Les complications cliniques de ce premier type sont inhabituelles. Le type II est plus grave et il sera le point de mire du présent article. Cinq patients recevant de l'héparine ont développé une TIH de type II ayant résulté, dans certains cas, en des complications menant à l'amputation d'un membre ou même, à la mort. DISCUSSION Chez un patient recevant de l'héparine, le développement de thrombocytopénie devrait alerter l'équipe soignante à la possibilité de TIH. Le traitement rapide de la TIH peut aider à prévenir les complications. Suivant une première exposition à l'héparine, la TIH se manifeste généralement 5–8 jours après le début du traitement. Le décompte plaquettaire diminue habituellement à moins de 100 times 103/mm3. Par la suite, il se normalise en 5–7 jours après l'arrêt du traitement à l'héparine. Malgré la thrombocytopénie, une thrombose ou de la coagulation intravasculaire disséminée peuvent se produire. Le traitement peut se subdiviser selon trois situations cliniques: thrombocytopénie légère à modérée asymptomatique, thrombocytopénie grave avec un compte de plaquettes moins de 50 times 103/mm3, et TIH compliquée de thromboembolie. CONCLUSIONS La TIH est une complication rare, potentiellement grave, et parfois fatale de l'héparinothérapie. Ainsi, lorsqu'un patient reçoit de l'héparine, le clinicien doit surveiller l'apparition de TIH, afin de la reconnaître de façon précoce et de la traiter adéquatement avant l'apparition de complications graves.


1989 ◽  
Vol 109 (3) ◽  
pp. 1363-1369 ◽  
Author(s):  
B Swoboda ◽  
R Holmdahl ◽  
H Stöss ◽  
K von der Mark

Collagen type XI is a component of hyaline cartilage consisting of alpha 1(XI), alpha 2(XI), and alpha 3(XI) chains; with 5-10% of the total collagen content, it is a minor but significant component next to type II collagen, but its function and precise localization in cartilaginous tissues is still unclear. Owing to the homology of the alpha 3(XI) and alpha 1(II) collagen chains, attempts to prepare specific antibodies to native type XI collagen have been unsuccessful in the past. In this study, we report on the preparation and use for immunohistochemistry of a polyclonal antibody specific for alpha 2(XI) denatured collagen chains. The antibody was prepared by immunization with the isolated alpha 2(XI) chain and reacts neither with native type XI collagen nor type I, II, V, or IX by ELISA or immunoblotting, nor with alpha 1(XI) or alpha 3(XI), but with alpha 2(XI) chains. Using this antibody, it was possible to specifically localize alpha 2(XI) in cartilage by pretreating tissue sections with 6 M urea. In double immunofluorescence staining experiments, the distribution of alpha 2(XI) as indicative for type XI collagen in fetal bovine and human cartilage was compared with that of type II collagen, using a monoclonal antibody to alpha 1(II). Type XI collagen was found throughout the matrix of hyaline cartilage. However, owing to cross-reactivity of the monoclonal anti-alpha 1(II) with alpha 3(XI), both antibodies produced the same staining pattern. Cellular heterogeneity was, however, detected in monolayer cultures of human chondrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


2005 ◽  
Vol 24 (5) ◽  
pp. 33-37 ◽  
Author(s):  
Julie Martchenke ◽  
Lynn Boshkov

Heparin-induced thrombocytopenia (HIT), an immune-mediated response to heparin administration, has been recognized in adults for some time, but only recently recognized in neonates and children. HIT Type I is a mild, self-limiting condition. HIT type II is a severe immune reaction to heparin that leads to thrombocytopenia and often thromboembolic complications. The incidence of HIT Type II is 2–5 percent in adults on heparin products and may be as high in neonates and children. The mortality rate from HIT in adults is 7–30 percent and is unknown but potentially high in newborns as well. The cardinal sign of HIT is a drop in platelet count by 50 percent or platelet counts below 70,000–100,000/mm3. This drop usually occurs five to ten days after the first exposure to heparin. Treatment is immediate cessation of all heparin therapy and initiation of alternative anticoagulants, especially the direct thrombin inhibitors lepirudin and argatroban. This article reviews the literature on HIT and presents a case of neonatal HIT following heart surgery.


1997 ◽  
Vol 3 (1) ◽  
pp. 58-62 ◽  
Author(s):  
Sherif S. Farag ◽  
Heten Savoia ◽  
Cindy J. O'Malley ◽  
Katherine M. McGrath

Alternative anticoagulation in patients with heparin-induced thrombocytopenia (HIT) is often problematic. The relatively high cross-reactivity rate reported for the low-molecular-weight heparins (LMWH) has discouraged their use in this setting. This study has investigated the safety of using the LMWH Fragmin, based on a negative heparin-dependent platelet aggregation test using the latter, in patients with proven HIT. Fifty-three evaluable patients with clinical and laboratory evidence of HIT were evaluated for cross-reactivity with Fragmin using a Fragmin-dependent platelet aggregation test. In 20 of 38 patients who showed no in vitro cross-reactivity. Fragmin was substituted for unfractionated heparin. The outcome of these 20 patients was evaluated and compared to that of the remaining 33 patients, in whom anticoagulates were ceased or warfarin or Orgaran was used. Eighteen of 20 patients treated with Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 57.9 ± 4.7 x 109/l within 2.8 ± 0.29 days following substitution of Fragmin for unfractionated heparin. Twenty-eight of the 33 remaining patients who did not receive Fragmin increased their platelet count by ≥50 x 109/l from a mean nadir of 53.0 ± 4.8 x 109/l within 3.0 ± 0.29 days. In seven patients (two treated with Fragmin), response could not be evaluated due to death within 36 h of cessation of heparin or discharge from hospital. The results indicate that in vitro cross-reactivity testing employing a heparin-dependent platelet aggregation assay can be safely used to select patients with HIT for further anticoagulation with LMWH. Key Words: Fragmin—Crossreactivity—Heparin-induced thrombocytopenia.


1988 ◽  
Vol 118 (2) ◽  
pp. 306-313 ◽  
Author(s):  
Sylvia van Buul-Offers ◽  
C. M. Hoogerbrugge ◽  
T. L. de Poorter

Abstract. Binding of labelled IGF-I and IGF-II was studied to bovine, ovine and human placental cell membranes. The data show a preponderance of type I receptors in human placental membranes, and of type II receptors in ovine placental membranes, confirming reported data. In contrast, bovine placental membranes are rich in both type I and type II receptors. Therefore, the bovine placenta offers a good model for measuring specifically IGF-I (cross-reactivity with IGF-II 7%) and IGF-II (cross-reactivity with IGF-I 4%). By Scatchard analysis the apparent Kd (1–1.36 nmol/l) for the high affinity binding sites of the type I receptor is similar in all three preparations. Total binding capacity in ovine placental membranes is, however, 4 times lower. The affinity for the type II receptor is lower than for type I, whereas total binding capacity is higher. Affinity cross-linking confirms the competition experiments, showing binding of IGF-I to typical type I and of IGF-II to type II receptors.


1984 ◽  
Vol 81 (23) ◽  
pp. 7579-7583 ◽  
Author(s):  
T. H. Lee ◽  
J. E. Coligan ◽  
M. F. McLane ◽  
J. G. Sodroski ◽  
M. Popovic ◽  
...  

2002 ◽  
Vol 15 (4) ◽  
pp. 305-317
Author(s):  
Sallie K. Young

Heparin, in various forms, is used in a variety of conditions including prophylaxis and treatment of thromboembolic disorders. Although the most common adverse effect related to the use of heparin is bleeding, heparin-induced thrombocytopenia (HIT) can also occur. Two types of HIT exist, HIT type I and type II. HIT type I is a mild and self-limiting disease in which the patient’s platelet count may decrease slightly but will recover with continued treatment. This is in contrast to HIT type II, which may lead to potentially devastating complications. Patients with HIT type II are at increased risk for thromboembolic complications that are mediated through autoimmune reactions and therefore require anticoagulation with danaparoid or one of the direct thrombin inhibitors, including lepirudin, argatroban, or bivalirudin. Limited data are available on the use of these agents in special populations including patients who are pregnant or those undergoing procedures such as percutaneous coronary intervention, cardiopulmonary bypass and dialysis, and pregnancy. Future therapies may include the use of unfractionated heparin in combination with glycoprotein IIb/IIIa inhibitors during cardiopulmonary bypass.


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