Refractory thrombocytopenia during liver transplantation requiring splenectomy

Abstract

Although thrombocytopenia is common in end-stage liver disease, severe, refractory thrombocytopenia during liver transplantation is rare, and if immune based, usually presents months or years later. This case describes an adult woman in whom preoperative evaluation had not determined an immune-related cause of thrombocytopenia. Clot strength was dramatically impaired as measured by thrombelastography during the transplant. Following a lack of response to repeat platelet transfusions, splenectomy was performed after graft reperfusion with rapid temporal restoration of clot strength. This case shows a severe manifestation of perioperative thrombocytopenia during liver transplantation and clinically guided management when measured clot strength is too low for accurate determination.

Thrombocytopenia is common in patients undergoing liver transplantation (LT), and causes include myelosuppression, splenic sequestration, and inadequate thrombopoietin.^1,2 Severe intraoperative thrombocytopenia with no clot strength on thrombelastography, refractory to platelet support, is rare. Nonhepatic causes include immune based, with sparse reports of immune thrombocytopenic purpura (ITP) months to years after LT and two cases of early postoperative presentation.^3–5 We describe a patient undergoing LT where an immune cause for thrombocytopenia was not found, who had persistent severe thrombocytopenia refractory to platelet transfusion with immeasurable indices of clot strength. Clot strength and bleeding improved dramatically after splenectomy done after revascularization. Partial or total splenectomy during LT is infrequently described for hypersplenism and to prevent complications from small-for-size grafts in living donor transplants.^6,7 A single report of simultaneous splenectomy for ITP in a patient with primary sclerosing cholangitis did not provide details of intraoperative management or viscoelastic hemostatic testing.⁸

CASE DESCRIPTION

A 67-year-old woman with decompensated hepatitis C virus cirrhosis (treated, with sustained viral response), pancytopenia, and severe thrombocytopenia presented with a Model for End-Stage Liver Disease score of 24, debilitating ascites, hydrothoraxes, and hepatic encephalopathy. Her platelet count was 15,000/mm³, with poor response to platelet transfusions. The etiology of thrombocytopenia was unclear: bone marrow biopsy and flow cytometry revealed no infiltrative process, the spleen was not enlarged, and there was no response to short courses of dexamethasone and intravenous immunoglobulin. A trial of avatrombopag was planned but had not been initiated when an organ became available and multidisciplinary consensus was to proceed with the transplant.

Laboratory values after anesthetic induction were a platelet count of 33,000/mm³, international normalized ratio of 2.0, and fibrinogen of 141 mg/dL. The TEG 6s (Thrombelastograph, Haemoscope, Braintree, MA) revealed severely impaired clot strength: a maximum amplitude < 40 mm, which was effectively < 20 mm since the signal did not generate a K time (time to 20 mm threshold). Neither functional fibrinogen (Figure 1) or platelet mapping was measurable. Repeated platelet and cryoprecipitate transfusions did not correct clot strength or clinical oozing. This was complicated by fibrinolysis after reperfusion, which was challenging to detect given the extremely low maximum amplitude (Figure 2), and corrected after epsilon aminocaproic acid treatment.

Figure 1.

Initial TEG 6s after anesthetic induction.

Figure 2.

TEG 6s trace with fibrinolysis superimposed on poor clot strength.

Although metabolic (correction of acidosis) and hemodynamic indices (weaning vasopressor infusions) improved, there was no change in TEG parameters. Given ongoing oozing, splenectomy was performed, after which TEG indices improved promptly, although they were slightly abnormal (Figure 3). Transfusion included 2 units of red blood cells, 1 unit of cell-saved blood, and 2 units of fresh frozen plasma with 6 platelet packs and 4 doses of cryoprecipitate. The postoperative course was uneventful without bleeding. The platelet count was 29,000 to 46,000/mm³ for 4 days. Aspirin and clopidogrel were started, and the platelet count increased to 300,000/mm³ at discharge on day 14. The patient is doing well with a functioning graft.

Figure 3.

Postsplenectomy TEG 6s with improved clot strength.

DISCUSSION

Severe thrombocytopenia (platelet count < 50,000/mm³) is frequent in patients for LT.¹ Causes include splenic sequestration, myelosuppression (toxins or viral disease), or inadequate thrombopoietin.² Immune causes are rare. ITP (idiopathic if no definitive cause) has premature removal of platelets when bound to nonspecific platelet antibody. It is rarely reported after LT,³ and there are two reports of early postoperative presentation on days 1 and 16, but none intraoperatively.^4,5 In this case, an immune cause was not identified, with no response to a short course of steroids or immunoglobulin. Thrombopoietin agonists, helpful for thrombocytopenia and ITP, had not been initiated before an organ become available. Given no definite diagnosis of ITP, the consensus was to proceed with transplant.

Visco-elastic coagulation monitoring is recommended to aid diagnosis and management of complex coagulation changes during LT.^9,10 The TEG 6s showed extremely low clot strength, which did not reach the threshold (20 mm) to generate a K time despite repeated platelet transfusions. The low laboratory and functional fibrinogen did not respond to repeated cryoprecipitate administration. Given continued bleeding and inadequate response to transfusion, a splenectomy was done with temporal improvement in clot strength and cessation of bleeding.

This case highlights severe, refractory thrombocytopenia during LT, unresponsive to platelet transfusion. Assessment is challenging when clot strength is so poor to make platelet and fibrinogen contributions to clot strength immeasurable on thrombelastography. Visco-elastic testing was useful to allow a focus on clot strength, rather than indiscriminate use of pro-hemostatic agents. Post-reperfusion fibrinolysis, superimposed on the very low maximum amplitude, allowed for targeted antifibrinolytic therapy at that time.