Preoperative Heparin Therapy Causes Immune-Mediated Hypotension Upon Heparin Administration for Cardiac Surgery

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.

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Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review

Thrombosis and Haemostasis ◽

10.1160/th17-03-0212 ◽

2017 ◽

Vol 117 (10) ◽

pp. 1868-1874 ◽

Cited By ~ 7

Author(s):

Jo-Ann Sheppard ◽

Theodore Warkentin ◽

Andrew Shih

Keyword(s):

Platelet Count ◽

Additional Patient ◽

Heparin Induced Thrombocytopenia ◽

Prophylactic Dose ◽

Heparin Administration ◽

Immune Mediated ◽

Antibody Levels ◽

Count Recovery

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.

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Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT

Perfusion ◽

10.1177/0267659117692661 ◽

2017 ◽

Vol 32 (6) ◽

pp. 474-480 ◽

Cited By ~ 4

Author(s):

Junko Ichikawa ◽

Tetsu Mori ◽

Mitsuharu Kodaka ◽

Keiko Nishiyama ◽

Makoto Ozaki ◽

...

Keyword(s):

Cardiac Surgery ◽

Platelet Count ◽

Dose Response ◽

Complete Blood Count ◽

Activity Level ◽

Heparin Dose ◽

Dose Requirement ◽

Heparin Concentration ◽

Heparin Administration

Introduction: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. Methods: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. Results: The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland–Altman analysis. Conclusion: It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

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Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽

10.1182/asheducation-2009.1.225 ◽

2009 ◽

Vol 2009 (1) ◽

pp. 225-232 ◽

Cited By ~ 14

Author(s):

Thomas L. Ortel

Keyword(s):

Platelet Count ◽

Heparin Therapy ◽

Severe Thrombocytopenia ◽

Drug Induced ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Immune Mediated ◽

Number Of Patients ◽

Increased Risk ◽

Antibody Levels

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.

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A case of heparin induced thrombocytopenia managed by Rivaroxaban

10.22541/au.163815973.39376126/v1 ◽

2021 ◽

Author(s):

Ali Eshraghi ◽

Faeze Keihanian

Keyword(s):

Cardiac Surgery ◽

Oral Anticoagulant ◽

Heparin Induced Thrombocytopenia ◽

Heparin Administration ◽

New Oral Anticoagulant ◽

Increased Risk

Heparin-induced thrombocytopenia (HIT) is an immunogenic disorder. It can lead to thrombocytopenia and a hypercoagulated state with an increased risk for new thrombosis. We here reported a 49-year-old man with previous cardiac surgery and heparin administration, treated by new oral anticoagulant agent, Rivaroxaban.

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Histamine blockade and cardiovascular changes following heparin administration during cardiac surgery

Journal of Cardiothoracic Anesthesia ◽

10.1016/s0888-6296(09)90009-6 ◽

1990 ◽

Vol 4 (6) ◽

pp. 711-714 ◽

Cited By ~ 17

Author(s):

Pierre A. Casthely ◽

Dushana Yoganathan ◽

Bill Karyanis ◽

Mary Salem ◽

Thil Yoganathan ◽

...

Keyword(s):

Cardiac Surgery ◽

Cardiovascular Changes ◽

Heparin Administration

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Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery

Perfusion ◽

10.1177/0267659120926089 ◽

2020 ◽

pp. 026765912092608

Author(s):

Alfred H Stammers ◽

Stephen G Francis ◽

Randi Miller ◽

Anthony Nostro ◽

Eric A Tesdahl ◽

...

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Heparin Therapy ◽

Sensitivity Index ◽

Transfusion Rate ◽

Clotting Time ◽

Activated Clotting Time ◽

Institutional Review ◽

Number Of Factors ◽

Heparin Resistance

The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg−1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin−1 IU kg−1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg−1 vs. 677.5 ± 199.0 IU kg−1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg−1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

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Treatment Of Venous Thromboembolism: Case For Heparin

10.1055/s-0038-1652737 ◽

1981 ◽

Author(s):

D Deykin

Keyword(s):

Major Complication ◽

Heparin Therapy ◽

High Dose ◽

Clotting Factors ◽

Close Attention ◽

Antithrombotic Drug ◽

Routes Of Administration ◽

Dose Heparin ◽

Heparin Administration

Heparin is the only antithrombotic drug whose efficacy has been uniquivocally established *by controlled prospective studies. The premise of heparin therapy, whether the drug is given by intravenous or subcutaneous routes of administration is the same: that by accelerating the inactivation of activated clotting factors the deposition or growth of stasis thrombi is inhibited. The major complication of heparin therapy, bleeding, can be reduced but not prevented by close attention to details of administration and monitoring. Thrombocytopenia, another complication of heparin, may be more frequent than previously suspected. Osteoporosis, a consequence of long-term, high-dose heparin administration, occurs when doses in excess of 10,000 units/day are administered for more than a few months. Properly given and monitored, heparin remains the standard against which all other forms of antithrombotic therapy should be measured.

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What Is the Best Time to Initiate Peri-Operative Heparin Therapy In General Surgery Patients? A Risk-Benefit Dilemma.

Blood ◽

10.1182/blood.v116.21.1088.1088 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1088-1088

Author(s):

Nassir Rostambeigi ◽

Susan Greenlee ◽

Marianne Huebner ◽

David Farley

Keyword(s):

Hospital Stay ◽

General Surgery ◽

Conflicts Of Interest ◽

Conditional Logistic Regression ◽

Length Of Hospital Stay ◽

Heparin Therapy ◽

Control Group ◽

Optimal Timing ◽

Bleeding Events ◽

Heparin Administration

Abstract Abstract 1088 Background: While many studies support the use of prophylactic heparin therapy around the time of operation in cancer patients, little data shows the optimal timing of such therapy in general surgery (GS) patients. Methods: From 2001–2008, 95 patients identified with thromboembolism reported in our GI/General Surgery Division and were compared with a matched control group for: age, gender, type of operation, date of operation, diagnosis of malignancy, and BMI. Timing of heparin therapy, characteristics of TE or bleeding events, driving distance from our institution, history of smoking or OCP use, anticoagulation use after operation, length of hospital stay, and mortality were collected. Peri-operative heparin therapy was defined as heparin given within a 24 hr window of incision. The McNemar's test for proportions was performed. Conditional logistic regression was used for the analysis of risk factors and survival curves were implemented for mortality comparisons. Results: mean age and BMI were similar (57 yrs, 33 kgM-2), 45% were female and 53% had malignancy in both groups. Duration of operation was similar (204 vs. 191 minutes, P=NS). peri-operative heparin administration was similar in the two groups (56%, 64%, p=0.05). But, pre-operative therapy was seen more in the control group (77% vs. 51%, p=0.01). Regression model showed a protective effect for heparin if it was given pre-operatively (OR=0.37, p=0.047) with no effect if it was given beyond 10 hours. Mean blood transfusion units (97 and 106 mL) and hemorrhagic events (4.5% and 5%) were similar (p=NS). Median (range) length of hospital stay was longer (19 days (0-201) vs. 6 (0-66), p=0.001) and two-year survival lower in the TE group (p=0.03). Conclusions: data from our institutional case-control study shows that heparin administration before GS is associated with more than 2-fold reduction in the risk of thromboembolism. The optimal period appears to be between 1–10 hours prior to the time of incision. Large prospective trials need to be desgined to more accurately determine the time of heparin therapy. Disclosures: No relevant conflicts of interest to declare.

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