Faculty of 1000 evaluation for Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.

AbstractIn both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.

Download Full-text

Decreased Bleeding Incidence with Direct Oral Anticoagulants Compared to Vitamin K Antagonist and Low-Molecular-Weight Heparin in Patients with Sickle Cell Disease and Venous Thromboembolism

Acta Haematologica ◽

10.1159/000500223 ◽

2019 ◽

Vol 142 (4) ◽

pp. 233-238 ◽

Cited By ~ 6

Author(s):

Ameet Patel ◽

Hants Williams ◽

Maria R. Baer ◽

Ann B. Zimrin ◽

Jennie Y. Law

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Sickle Cell Disease ◽

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Low Molecular Weight ◽

Cell Disease ◽

Bleeding Events

Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD), yet the optimal pharmacologic anticoagulant is unknown. Methods: A retrospective single-institution cohort study of patients with SCD complicated by first VTE from January 2009 through July 2017 was performed using ICD 9/10 codes. Data collected included the anticoagulant used, VTE recurrence, and incidence of bleeding. Results: 109 patients with VTE were identified. SCD genotypes included HbSS in 92 (84%), HbSC in 13 (12%), and HbS-β+ thalassemia in 4 (4%). After the initial VTE event, 32 patients received a vitamin K antagonist (VKA), 34 for low-molecular-weight heparin (LMWH), and 43 for direct oral anticoagulants (DOACs). 16 patients (15%) experienced a clinically significant bleeding event, including 9 on VKA, 5 on LMWH, and 2 on DOACs. At a median follow-up of 11.8 (range, 3.4–60) months, 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH, and 13 on DOACs (p = 0.833). Bleeding incidence was least with the DOACs, which were associated with fewer bleeding events (OR 0.22), and greatest with VKA (OR 1.55) (p < 0.05). Conclusion: There was no difference between VTE recurrence and choice of anticoagulation in SCD patients with VTE. Bleeding events were lower for DOACs compared to VKA or LMWH.

Download Full-text