Israel Medical Association Journal

Background: Unfractionated heparin is the preferred anticoagulant used during open heart surgeries, including left ventricular assist device (LVAD) implantation. In cases in which patients are heparin-induced thrombocytopenia positive (HIT+), the accepted practice has been to substitute heparin with bivalirudin. This practice may be associated with significant bleeding and adverse outcomes.

Objectives: To review our experience with HIT+ patients who were heparin-induced thrombocytopenia with thrombosis negative (HITT-) and who underwent HeartMate 3 LVAD implantation using heparin intraoperatively rather than bivalirudin.

Methods: From 2016 to 2022, 144 adult patients were implanted with HeartMate 3 LVAD at our center. Among them, 7 were detected as HIT+ but HITT- and therefore were prescribed intraoperatively with heparin and treated pre- and postoperatively with bivalirudin. We reviewed the preoperative, intraoperative, and postoperative characteristics as well as short-term mortality and the complication rates of these HIT+ patients.

Results: The median age of our cohort was 56 years (51–60), 71% were male (n=5), all were INTERMACS Level 1, and most were bridged to transplant (n=6, 86%). The 30-day mortality rate post-implantation was 0%. The average 24-hour chest drain postoperative output was 1502.86 ± 931.34 ml. There were no intraoperative pump thromboses, perioperative thromboses, cerebrovascular accidents, or gastrointestinal bleeding within the first 24 hours postoperative. One patient required a revision due to bleeding.

Conclusions: Intraoperative unfractionated heparin may be administered to patients who are HIT+ and HITT- while undergoing LVAD implantation. However, further investigation is required.

Background: Fibromyalgia syndrome (FMS) is estimated to affect 2–4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN.

Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls.

Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique.

Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013).

Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Background: The management of aspirin therapy before an invasive procedure poses a frequent clinical dilemma due to uncertainty regarding b[AS1] leeding versus thromboembolic risks associated with continuation or withdrawal of the drug. There is no evidence-based data to refer to.

Objectives: To assess the opinions of internal medicine physicians regarding aspirin therapy prior to an invasive procedure.

Methods: A questionnaire presenting nine hypothetical cases with different combinations of bleeding and thromboembolic risk was given to physicians in an Internal Medicine Division during a personal interview. For each case the participants had to choose between withdrawal of aspirin prior to an invasive procedure, continuation of aspirin, or substitution of low molecular weight heparin for aspirin. Results: Sixty-one physicians participated in the survey. For a patient with low thromboembolic risk, 77% (95% confidence interval 65.3–86.3%), 95% (87.2–98.7%) and 97% (89.6–99.5%) of physicians elected to discontinue aspirin prior to a low, intermediate or high bleeding risk procedure, respectively. For intermediate risk patients, 23% (95% CI[1] 13.7–34.7%), 59% (46.4–70.8%) and 74% (61.7–83.6%) would discontinue aspirin prior to a low, intermediate or high risk procedure, and 5% (95% CI 1.3–12.8%), 23% (13.7–34.7%) and 18% (9.9–29.2%) would substitute LMWH[2] for aspirin. For a patient with high thromboembolic risk, 1.6% (95% CI 0.08–7.8%), 11.5% (5.2–21.4%) and 18% (9.9–29.2%) recommended discontinuing aspirin prior to a low, intermediate or high risk procedure, respectively. In these situations, 18% (95% CI 9.9–29.2%), 53% (40.0–64.7%) and 57% (44.8–69.3%), respectively, would substitute LMWH for aspirin.

Conclusions: The results of the current investigation may help practicing physicians to decide whether to discontinue aspirin therapy prior to invasive procedures. The possible use of LMWH to replace aspirin as suggested here should be further evaluated in a controlled clinical study.

 

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

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[1] LMW = low molecular weight

[2] VTE = venous thromboembolism