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

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 2955-2959 ◽  
Author(s):  
Bruno Girolami ◽  
Paolo Prandoni ◽  
Piero M. Stefani ◽  
Cinzia Tanduo ◽  
Paola Sabbion ◽  
...  
Keyword(s):  
Platelet Count ◽  
Unfractionated Heparin ◽  
Odds Ratio ◽  
Thromboembolic Complication ◽  
High Rate ◽  
Clinical Settings ◽  
Medical Patients ◽  
Thromboembolic Complications ◽  
Heparin Induced Thrombocytopenia ◽  
Medical Wards

Abstract Although 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.

Immobilization and high platelet count are associated with thromboembolic complications in heparin-induced thrombocytopenia

2017 ◽  
Vol 26 (10) ◽  
pp. 1149-1155 ◽  
Author(s):  
Juliane Bolbrinker ◽  
Edeltraut Garbe ◽  
Antonios Douros ◽  
Matthias Huber ◽  
Elisabeth Bronder ◽  
...  
Keyword(s):  
Platelet Count ◽  
Thromboembolic Complications ◽  
Heparin Induced Thrombocytopenia ◽  
High Platelet Count

Treatment of Heparin-Induced Thrombocytopenia

1999 ◽  
Vol 82 (08) ◽  
pp. 457-467 ◽  
Author(s):  
Andreas Greinacher
Keyword(s):  
Molecular Weight ◽  
Plasma Proteins ◽  
Cell Types ◽  
Thromboembolic Complication ◽  
Clinical Settings ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Marked Variability ◽  
Heparin Complexes ◽  
Anticoagulant Response

IntroductionUnfractionated heparin (UFH) and low molecular weight heparin (LMWH) are the most widely used anticoagulants when parenteral anticoagulation with a short half-life is required. Both can be administered subcutaneously and intravenously, and both have been shown to be effective in a variety of clinical settings.1 UFH has several limitations. One is its poor bioavailability after subcutaneous injection and the marked variability in its anticoagulant response in patients with an acute thromboembolic complication.2,3 Another major issue associated with UFH is the induction of heparin-induced thrombocytopenia (HIT). Both limitations are closely linked,4 as the underlying cause is the high density of negative charges on the heparin molecule and its molecular weight. Both are responsible for the binding of heparin to plasma proteins other than antithrombin (AT), such as platelet factor 4 (PF4) and to several cell types. This leads to heparin-platelet interaction, the formation of HIT antigen (i.e., PF4/heparin complexes), and inhibition of the anticoagulant effect of heparin (aPTT-nonresponder).

scholarly journals Viscoelastic Tests in the Evaluation of Haemostasis Disturbances in SARS-CoV2 Infection

2020 ◽  
Vol 33 (13) ◽  
Author(s):  
Anabela Rodrigues ◽  
Teresa Seara Sevivas ◽  
Carla Leal Pereira ◽  
André Caiado ◽  
António Robalo Nunes
Keyword(s):  
Platelet Count ◽  
Clinical Status ◽  
High Rate ◽  
Clinical Settings ◽  
Bleeding Events ◽  
Anticoagulation Management ◽  
Laboratory Findings ◽  
Thrombotic Risk ◽  
Reactive Protein ◽  
Coagulation Tests

COVID-19 associated coagulopathy is a dysfunction of severe SARS-CoV-2 infection, characterized by significantly increased fibrinogen, D-dimer and C reactive protein and normal to near-normal prothrombin time, activated partial thromboplastin time and platelet count. Hypercoagulopathy and hypofibrinolysis coexist and are detected by viscoelastic tests. These features, when associated with immobilization and intrinsic risk factors (age, obesity, comorbidities, drugs) of the patient, can trigger thromboembolic events, despite thromboprophylaxis. The lungs are the first and most severely damaged organ. To date, most patients have exhibited hypercoagulability on viscoelastic tests not detected by standard coagulation tests. A high rate of thrombotic events was reported, suggesting that it should be considered as a cause of clinical deterioration in intensive care and potentially other clinical settings. In advanced stage, COVID-19 associated coagulopathy, fibrinogen and platelet count can decrease significantly, depending on the severity of clinical status resembling consumptive coagulopathy. In this stage, bleeding events can occur, especially if the patient is under extracorporeal membrane oxygenation (ECMO). Viscoelastic tests are very useful tools to assess hypercoagulability and hypofibrinolysis (not detectable by standard coagulation tests) in critically ill SARS-CoV-2 patients with COVID-19 associated coagulopathy and look like very promising tools for anticoagulation management. However, further research needs to be carried out to determine whether abnormal viscoelastic tests alone or in combination with other clinical or laboratory findings can identify patients at increased thrombotic risk. Clinical trials to evaluate hypercoagulability using viscoelastic tests and the need for personalized dosage of anticoagulation in SARS-CoV-2 patientsare quickly emerging.

A Meta-Analysis to Determine the Risk of Heparin Induced Thrombocytopenia (HIT) and Isolated Thrombocytopenia in Prophylaxis Studies Comparing Unfractioneted Heparin (UFH) and Low Molecular Weight Heparin (LMWH).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2587-2587 ◽  
Author(s):  
Nadine Martel ◽  
Philip S. Wells
Keyword(s):  
Molecular Weight ◽  
Odds Ratio ◽  
Low Molecular Weight Heparin ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Low Molecular Weight ◽  
Medical Patients ◽  
Heparin Induced Thrombocytopenia ◽  
Significant Difference

Abstract HIT is an uncommon but potentially devastating complication of anticoagulation with UFH or LMWH. The absolute risk of HIT and thrombocytopenia are not clearly defined and no summary data to provide odds ratio is available. We conducted a meta-analysis to determine and compare the incidences of HIT in surgical or medical patients receiving thromboprophylaxis with either UFH or LMWH. We searched MEDLINE-OVID and MEDLINE-PubMed using and combining the following terms: heparin induced thrombocytopenia, low molecular weight heparin, prophylaxis, randomized controlled trials, prospective studies. The function Explode was used. Search was limited to humans from 1984 to 2004. Over 400 abstracts were reviewed and then 91 articles were independently reviewed by two authors, without any restriction of article language. Included studies were those comparing prophylactic UFH and LMWH and measuring HIT (defined as platelets drop > 50% or < 100 X 109/L AND positive laboratory HIT assay) or thrombocytopenia (defined as platelets drop > 50% or < 100 X 109/L) as outcomes. Studies defining thrombocytopenia with lower thresholds were excluded because cases could have been missed. Extracted data included patient characteristics, drug regimens, HIT, thrombocytopenia and venous thromboembolism rates. Disagreements were resolved by consensus. Eligible studies were included into the meta-analysis using a random-effects model to determine the odds ratio for the incidences of HIT and thrombocytopenia between UFH and LMWH. Funnel plots were made to assess possible publication bias. 17 articles were eligible with a total of 8500 patients: 2 RCTs measuring HIT; 10 RCTs measuring thrombocytopenia, and 5 prospective non-randomized studies with comparison groups measuring HIT. Three analysis were performed and all favoured the use of LMWH: 1) 2 RCTs measuring HIT showed an OR of 0.10 (95% confidence interval [CI] 0.01–0.77; p=0.03); 2) all 7 studies measuring HIT showed an OR of 0.11 (95%CI= 0.05–0.26; p< 0.00001); 3) 12 RCTs measuring thrombocytopenia showed an OR of 0.45 (95% CI= 0.26–0.80; p=0.006). Comparing the rates in the 7 studies measuring HIT UFH resulted in HIT in 3.4% (95%CI=2.6% to 4.3%) of cases and LMWH resulted in HIT in 0.2% (95% CI=0.1% to 0.6%), a statistically significant difference (p<0.0001). This meta-analysis confirms the lower incidences of HIT and thrombocytopenia with LMWH prophylaxis compared to UFH. Absolute rates of HIT with LMWH are very low. The HIT rates should be considered when determining the drug of choice for thromboprophylaxis in surgical and medical patients.

Lack of In Vitro Cross-Reactivity Predicts Safety of Low-Molecular Weight Heparins in Heparin-Induced Thrombocytopenia

1997 ◽  
Vol 3 (1) ◽  
pp. 58-62 ◽  
Author(s):  
Sherif S. Farag ◽  
Heten Savoia ◽  
Cindy J. O'Malley ◽  
Katherine M. McGrath
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Unfractionated Heparin ◽  
Cross Reactivity ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Aggregation Assay ◽  
Heparin Induced Thrombocytopenia

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.

ASH evidence-based guidelines: is the IgG-specific anti-PF4/heparin ELISA superior to the polyspecific ELISA in the laboratory diagnosis of HIT?

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 250-252 ◽  
Author(s):  
Adam Cuker ◽  
Thomas L. Ortel
Keyword(s):  
Differential Diagnosis ◽  
Platelet Count ◽  
Small Bowel ◽  
Unfractionated Heparin ◽  
Small Bowel Obstruction ◽  
Laboratory Testing ◽  
Laboratory Diagnosis ◽  
Evidence Based ◽  
Heparin Induced Thrombocytopenia ◽  
Evidence Based Guidelines

Abstract You are asked to consult on a 76-year-old man admitted to the hospital with pneumonia and thrombocytopenia. Ten days before the current admission, he had undergone surgery to repair a small bowel obstruction. A preoperative platelet count had been normal. Following surgery, he received subcutaneous unfractionated heparin thromboprophylaxis until his discharge on post-operative day 5. In your differential diagnosis for the patient’s thrombocytopenia, you consider heparin-induced thrombocytopenia (HIT) and wish to order laboratory testing. In addition to a polyspecific anti-PF4/heparin ELISA for the diagnosis of HIT, your laboratory has recently begun to offer an IgG-specific ELISA. You wonder which of these assays performs better in the diagnosis of HIT.

Heparin-induced Thrombocytopenia in Two Patients Undergoing Abdominal Aortic Aneurysm Surgery

2009 ◽  
Vol 16 (1) ◽  
pp. 110-114 ◽  
Author(s):  
Takaki Sugimoto ◽  
Takefumi Matsuo ◽  
Keiko Wanaka
Keyword(s):  
Platelet Count ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Unfractionated Heparin ◽  
Disseminated Intravascular Coagulation ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Intravascular Coagulation ◽  
Abdominal Aortic

We have experienced 2 cases of heparin-induced thrombocytopenia during unfractionated heparin treatment for disseminated intravascular coagulation after surgery for an abdominal aortic aneurysm. In the first case, as a symptom of disseminated intravascular coagulation gradually improved with antithrombin concentrates and heparin treatment, mesenteric artery thrombosis suddenly occurred, associated with a >50% decrease in platelet count on the 11th day. Although the platelet counts were increasing due to heparin cessation, clinical symptom and coagulation abnormalities worsened to multiple organ failure. In the second case, the platelet count decreased to <10 × 104/µL on the 13th day after the start of unfractionated heparin anticoagulation along with continuous hemodiafiltration, which was indicated for postoperative renal failure. The extracorporeal circuit clotted frequently under an adequate dose of unfractionated heparin. Serologically, heparin—platelet factor 4 complex antibodies were repeatedly detected by enzyme-linked immunosorbent assay. Argatroban, a direct thrombin inhibitor, was introduced as an alternative to unfractionated heparin, and the platelet count improved with a decrease in titers of the antibodies. Disseminated intravascular coagulation is a common complication in cases of abdominal aortic aneurysm and is usually treated in association with unfractionated heparin. It is important to recognize the onset of heparin-induced thrombocytopenia that acute declines in the platelet count and appearance of thrombosis with positive for heparin—platelet factor 4 complex antibodies would suddenly occur in clinical course of disseminated intravascular coagulation.

Fondaparinux for the treatment of patients with acute heparininduced thrombocytopenia

2008 ◽  
Vol 99 (01) ◽  
pp. 208-214 ◽  
Author(s):  
Christopher Finch ◽  
Amanda Howard ◽  
Sohail Minhas ◽  
Bob Lobo
Keyword(s):  
Platelet Count ◽  
Thromboembolic Complication ◽  
Limb Amputation ◽  
Thrombin Inhibitor ◽  
Primary Study ◽  
Thromboembolic Complications ◽  
Life Threatening ◽  
Delayed Recognition ◽  
Historical Controls ◽  
Count Recovery

SummaryHeparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm3 by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/ or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

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