Thrombocytopenia and liver transplantation

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Thrombocytopenia and liver transplantation

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Pre-op

• occurs in 15 to 70 of patients with cirrhosis of
  the liver
• 1/3 of circulating platelets are sequestered in
  the spleen
• Splenic sequestration of platelets can be
  increased to 90 in liver cirrhosis, portal
  hypertension, and splenomegaly

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• Except hypersplenism
• decreased production of platelets in bone marrow
  reticulated platelets
• reticulated platelets represent young ceils
  recently released from the bone marrow.
• The number of reticulated platelets in the
  peripheral blood reflects thrombopoiesis
• antibody-mediated destruction

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• Inadequate thrombopoietin (TPO) production
• TPO key regulator of thrombocyte production,
  almost exclusively produced by liver

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Post op

• common among orthotopic liver transplant (OLT)
  candidates and recipients.
• PLA fell significantly from preoperative levels
  by the first postoperative day
• postoperative bleeding or haemorrhagic
  complications

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• gradual reduce to a nadir on the 35th day after
  operation
• Recover within the first 2 weeks with subsequent
  platelet count increases by 1 month.

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• The median reticulated platelets reached its
  peak before PLT recover
• TPO may increasre 58 fold over baseline
• no significant changes in VWF, thrombomodulin
  ,E-selectin levels (Endothelial activation
  markers )

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• rise in prothrombin fragment F1.2 , followed by
  rises in fibrinogen and fibrin degradation
  products (secondary hyperfibrinolysis early after
  hepatectomy)
• increase in reticulated platelets after surgery
  may allow the prediction of allograft function

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multifactorial

• residual portal hypertension(intrahepatic
• and splenic congestion)
• reduced hepatic thrombopoietin production
• Hypersplenism
• reperfusion injury
• GVHD (graft vs. host disease )?allograft
  dysfunction

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• immediate cessation of entry of platelets into
  peripheral blood (Platelets were found to
  accumulate in the hepatic sinusoids of the
  remnant liver after hepatectomy)
• drug effects
• Chronic gastrointestinal bleeding
• intravascular hemolysis

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Thrombocytopenia

• Heparin-induced thrombocytopenia (HIT)
• druginduced thrombocytopenia
• viral infectionrelated thrombocytopenia
• idiopathic immune- mediated thrombocytopenic
  purpura (ITP)

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Heparin-induced thrombocytopenia

• four or more days use
• IgG IgM are provoked by the complex of heparin
  and platelet factor 4 (PF4)
• binds to platelet via the Fc portion, leads to
  platelet activationfurther release of PF4
  (positive feedback loop)
• The activated platelets aggregate(microparticle)
  and are removed prematurely from the circulation
  

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• heparin bound to platelet factor 4 (PF4) induces
  an antibody response. An IgG antibody directed
  against the heparin-PF4 complex binds platelets
  through the Fc receptor, leading to platelet
  activation and microparticle formation.
  Platelet-rich thrombi form at sites of
  preexisting pathology or sites of endothelial
  cell (EC) injury.

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Drug-induced thrombocytopenia

• Medications begun within 1 month are more likely
  to be the cause of the thrombocytopenia
• azathioprine and mycophenolate mofetil
• ganciclovir, valganciclovir, and trimethoprim
  sulfamethoxazole

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• accelerated platelet destruction caused by
  drug-dependent antibodies. The drug-dependent
  antibodies bind to platelets via their Fab
  regions
• react with glycoproteins GP Ib-IX, GP IIb/IIIa,
  GP V, platelet-endothelial cell adhesion
  molecule-1 (PECAM-1), or perhaps other platelet
  surface glycoproteins, causing a protein
  conformational change

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viral infectionrelated thrombocytopenia

• 10 HIV infection
• HHV-6
• cytomegalovirus (CMV)
• Herpes zoster
• Human parvovirus B19
• influenza A
• hepatitis C
• Dengue virus

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new-onset ITP

• severe unexplained thrombocytopenia remote from
  transplantation , 0.7
• primary biliary cirrhosis and primary sclerosing
  cholangitis are risk factor
• May Induce by calcineurin inhibitors cyclosporine
  and tacrolimus ( inadequate immunosuppression)

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Treatment

• many of these patients recover without specific
  treatment
• splenectomy may play a beneficial role ,most
  common in thrombocytopenia
• intravenous transfusions of immune globulin
• repeated platelet transfusions
• avoidance of drugs capable of inducing
  thrombocytopenia

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• repeated platelet transfusions
• avoidance of drugs capable of inducing
  thrombocytopenia
• Steroid
• serial rituximab infusions
• spleno-renal shunt
• Partial splenic embolization

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SPL

• post-transplant bleeding due to left-sided portal
  hypertension and Massive post-operative ascitic
  fluid loss
• reduction of allograft rejection
• idiopathic thrombocytopenic purpura
• spleen infarction after transplantation
• Prevention hemorrhage in patients with multiple
  splenic artery aneurysms.

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PSE

• unexplained post-operative ascites fluid loss due
  to functional graft congestion.
• prevent bleeding in liver transplant patients
  with small distal splenic artery aneurysms

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PSE vs SPL

• resolution of the complications of hypersplenism
• risks of overwhelming postsplenctomy sepsis
  (OPSS)
• nonoperative intervention (decrease morbidity and
  mortality)
• Postembolization syndrome fever, left quadrant
  pain, small left pleural effusion, and
  leukocytosis.

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ADMTS13

• If thrombocytopenia is combined with significant
  decrease of ADMTS13, liver graft function may be
  deteriorated due to microcirculatory disturbance.
  
• monitoring of ADAMTS13 is important to judge the
  necessity of treatment for thrombocytopenia

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ADMTS13

• a disintegrin-like and metalloproteinase with
  thrombospondin type-1 motifs 13
• cleaves the multimeric von Willebrand factor
  (VWF).
• Deficiency will increases the unusually large VWF
  multimers (UL-VWFM),leads to platelet clumping
  and/or thrombus formation, resulting in
  microcirculatory disturbance.
• FFP is the only available source of ADAMTS13
  replacement

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Thanks for your attention