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Walking a Thin Line

Published:October 13, 2022DOI:https://doi.org/10.1053/j.jvca.2022.10.008
      To the Editor:
      We congratulate Christophel-Plathier et al. for successfully managing complex coagulation issues in a patient with combined Bernard-Soulier syndrome and storage pool disease who underwent a replacement of ascending aorta and coronary artery bypass grafting during cardiopulmonary bypass.
      • Christophel-Plathier E
      • Costanza M
      • Bergman SA.
      Perioperative management of a patient with combined Bernard Soulier syndrome and storage pool disease during on-pump cardiac surgery [e-pub ahead of print].
      We would like to provide additional comments on the pathophysiology and clinical management of Bernard-Soulier syndrome and storage pool disease.
      First, prophylactic platelet transfusion was deemed important in this case that involved heparin anticoagulation for bypass, given the patient's history of numerous bleeding events after noncardiac surgeries. The authors documented the presence of grayish giant platelets in the blood smear, reduced glycoprotein Ib-V-IX complex, and severely reduced release from alpha and dense granules. A reduced formation of coated platelets (Collagen And Thrombin-activated platelets) on flow cytometry signifies the following: (1) platelets express less surface phosphatidylserine, which is a catalytic surface for thrombin generation; and (2) the platelet surface retains low amounts of procoagulant proteins including fibrinogen, factor V, and von Willebrand factors due to alpha-granule defects. The lack of glycoprotein Ib-V-IX complex or von Willebrand factors results in reduced prothrombin conversion to thrombin on platelets.
      • Beguin S
      • Keularts I
      • Al Dieri R
      • et al.
      Fibrin polymerization is crucial for thrombin generation in platelet-rich plasma in a VWF-GPIb-dependent process, defective in Bernard-Soulier syndrome.
      Therefore, hemostatic defects in Bernard-Soulier syndrome and storage pool disease involve both primary and secondary hemostasis.
      Second, their surgery was performed under normothermia, which presumably mitigated the severity of thrombocytopenia and coagulopathy after bypass.
      • Shenaq SA
      • Yawn DH
      • Saleem A
      • et al.
      Effect of profound hypothermia on leukocytes and platelets.
      Nevertheless, microvascular bleeding continued after platelet transfusion, and a subsequent contact-activated INTEM test demonstrated a grossly abnormal clotting time (CT, 348 s [normal 161-204 s]) and low 5-minute clot amplitude (A5, 30 mm [normal 33-52 mm]). HEPTEM (heparinase) CT also was prolonged (311 s). Thus, thrombocytopenia and coagulation factor deficiency were suspected despite normal fibrin polymerization (FIBTEM-A5, 13 mm). Prolongation of INTEM-CT previously was reported in congenital factor V deficiency.
      • Spiezia L
      • Radu C
      • Campello E
      • et al.
      Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V.
      In the current patient,
      • Christophel-Plathier E
      • Costanza M
      • Bergman SA.
      Perioperative management of a patient with combined Bernard Soulier syndrome and storage pool disease during on-pump cardiac surgery [e-pub ahead of print].
      alpha-granules were depleted, and the lack of platelet-derived factor V most likely contributed to prolonged INTEM-CT. The expected factor V recovery from 2 units of fresh frozen plasma is low (<5%),
      • Tanaka KA
      • VanDyck K
      • Shettar SS
      • et al.
      Perioperative management of hereditary factor V deficiency: Timing of plasma administration is critical in maximizing hemostatic potency of transfused factor V.
      and 4-factor prothrombin complex concentrate does not contain a therapeutic amount of factor V. Incomplete recovery of INTEM-CT (208 s), and moderate postoperative blood loss (1.35 L in 24 h) highlighted the major challenges in managing coagulopathy in this setting.
      Finally, the authors used tranexamic acid for antifibrinolytic therapy during bypass, and then resumed thromboprophylaxis using unfractionated heparin (10,000 units over 24 h), and oral tranexamic acid after surgery. It is important to emphasize that platelet alpha-granules contain plasminogen activator inhibitor-1, which antagonizes local plasminogen activator.
      • Huebner BR
      • Moore EE
      • Moore HB
      • et al.
      Thrombin provokes degranulation of platelet alpha-granules leading to the release of active plasminogen activator Inhibitor-1 (PAI-1).
      A profibrinolytic state is expected in the presence of thrombocytopenia and storage pool disease, which certainly justifies the authors’ use of tranexamic acid.

      Declaration of Competing Interest

      This work was supported in part by the Diversity and Inclusion grant from the Society of Cardiovascular Anesthesiologists. K.A.T. and K.V. have received research support from Cellphire (Rockville, MD).

      References

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        • Costanza M
        • Bergman SA.
        Perioperative management of a patient with combined Bernard Soulier syndrome and storage pool disease during on-pump cardiac surgery [e-pub ahead of print].
        J Cardiothorac Vasc Anesth. 2022; https://doi.org/10.1053/j.jvca.2022.09.078
        • Beguin S
        • Keularts I
        • Al Dieri R
        • et al.
        Fibrin polymerization is crucial for thrombin generation in platelet-rich plasma in a VWF-GPIb-dependent process, defective in Bernard-Soulier syndrome.
        J Thromb Haemost. 2004; 2: 170-176
        • Shenaq SA
        • Yawn DH
        • Saleem A
        • et al.
        Effect of profound hypothermia on leukocytes and platelets.
        Ann Clin Lab Sci. 1986; 16: 130-133
        • Spiezia L
        • Radu C
        • Campello E
        • et al.
        Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V.
        Haemophilia. 2012; 18: 463-468
        • Tanaka KA
        • VanDyck K
        • Shettar SS
        • et al.
        Perioperative management of hereditary factor V deficiency: Timing of plasma administration is critical in maximizing hemostatic potency of transfused factor V.
        J Cardiothorac Vasc Anesth. 2022; 36: 1811-1812
        • Huebner BR
        • Moore EE
        • Moore HB
        • et al.
        Thrombin provokes degranulation of platelet alpha-granules leading to the release of active plasminogen activator Inhibitor-1 (PAI-1).
        Shock. 2018; 50: 671-676

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