Heparin-Induced Thrombocytopenia

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.

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.


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.


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.


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.


2017 ◽  
Vol 117 (10) ◽  
pp. 1868-1874 ◽  
Author(s):  
Jo-Ann Sheppard ◽  
Theodore Warkentin ◽  
Andrew Shih

SummaryOne of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies (“seroreversion”). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.


2021 ◽  
Vol 22 (20) ◽  
pp. 11212
Author(s):  
Manuel Faúndez-Parraguez ◽  
Carlos Alarcón-Miranda ◽  
Young Hwa Cho ◽  
Hernán Pessoa-Mahana ◽  
Carlos Gallardo-Garrido ◽  
...  

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.


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


1981 ◽  
Author(s):  
S Moore ◽  
L W Belbeck ◽  
M Richardson

Damage to the luminal surface of an artery is associated with the development of platelet-fibrin thrombus or a monolayer of platelets. The first type of reaction (Type I) follows damage caused by an indwelling catheter or by repeated exposure of the endothelial surface to antibody. The second (Type 2) follows removal of the endothelium by a Fogarty balloon catheter. The reaction of the vessel wall to these two types of injury, while having many similar features, differs in a number of important respects. Both are dependant on the interaction of platelets with the vessel wall and can be suppressed or inhibited by inducing a severe thrombocytopenia using anti-platelet serum. In both, the thickness of lesions is related to repetitiveness of injury. Both are characterized by smooth muscle cell proliferation and lipid accumulation in normolipemic rabbits. The type I lesion regresses rapidly, losing size and lipid content, when the injury stimulus is removed. The Type 2 lesion persists and continues to accumulate lipid over timeIn the Type I lesion, induced by an indwelling aortic catheter, platelet consumption is increased for eight days and fresh platelet-fibrin thrombus may be found on the surface of the lesion months after placement of the catheter. Platelet survival is shortened. In the Type 2 lesion the initial interaction of platelets with the vessel wall is short lived, and the surface covering of platelets is rapidly lost. Platelet survival is not shortened in rabbits. While both lesions exhibit abundant accumulation of extracellular and intracellular lipid, this occurs earlier in the Type I lesion and disappears fairly rapidly when the Injury stimulus is removed. Lipid appears later in the Type 2 lesion, persists and increases in amount, even following a single injury. Fatty streaks, though observed in both types of injury, are more likely to be seen as a stage of regression of Type I lesions. The Type I lesion closely resembles the raised (complicated) lesion of human atherosclerosis. The Type 2 lesion resembles the human fibrous plaque. Supported by Grants MT-2168, M.R.C., 15-7 O.H.F.


2002 ◽  
Vol 9 (2_suppl) ◽  
pp. II-25-II-31 ◽  
Author(s):  
Xavier Kos ◽  
Louis Bouchard ◽  
Philippe Otal ◽  
Valérie Chabbert ◽  
Patricia Chemla ◽  
...  

Purpose: To evaluate the efficacy of stent-graft placement for the treatment of penetrating thoracic aortic ulcers. Methods: Ten patients (7 men; mean age 73.8 years, range 69–79) were treated for penetrating thoracic aortic ulcers using Talent or Excluder stent-grafts. Preoperative examinations included computed tomographic angiography (CTA), transesophageal echography, and digital subtraction angiography (DSA). Follow-up included predischarge multimodal imaging and periodic CTA scans after discharge. Endoleaks, aortic diameter changes, and clinical complications were tracked. Results: Technical success was achieved in 100%, but 1 major neurological complication led to death 3 months after the procedure. Radiological follow-up detected 4 early endoleaks (3 type I and a type II), all of which spontaneously regressed, and 1 secondary type II endoleak. The mean aortic diameter decreased by 22% over a mean 9-month follow-up. Conclusions: Aortic ulcers are potentially lethal lesions. Considering its low morbidity and mortality, endovascular repair could widen the treatment options for these lesions.


Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Andreas Greinacher ◽  
Kathleen Selleng

Abstract The many comorbidities in the severely ill patient also make thrombocytopenia very common (∼ 40%) in intensive care unit patients. The risk of bleeding is high with severe thrombocytopenia and is enhanced in intensive care patients with mild or moderately low platelet counts when additional factors are present that interfere with normal hemostatic mechanisms (eg, platelet function defects, hyperfibrinolysis, invasive procedures, or catheters). Even if not associated with bleeding, low platelet counts often influence patient management and may prompt physicians to withhold or delay necessary invasive interventions, reduce the intensity of anticoagulation, order prophylactic platelet transfusion, or change anticoagulants due to fear of heparin-induced thrombocytopenia. One approach to identify potential causes of thrombocytopenia that require specific interventions is to consider the dynamics of platelet count changes. The relative decrease in platelet counts within the first 3 to 4 days after major surgery is informative about the magnitude of the trauma or blood loss, whereas the dynamic of the platelet count course thereafter shows whether or not the physiologic compensatory mechanisms are working. A slow and gradual fall in platelet counts developing over 5 to 7 days is more likely to be caused by consumptive coagulopathy or bone marrow failure, whereas any abrupt decrease (within 1–2 days) in platelet counts manifesting after an initial increase in platelet counts approximately 1 to 2 weeks after surgery strongly suggests immunologic causes, including heparin-induced thrombocytopenia, other drug-induced immune thrombocytopenia, and posttransfusion purpura.


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