**1. Introduction**

Thrombocytopenia is a common complication of both chronic liver disease and liver transplantation (LT) contributing to the complex hemostasis disturbances of those patients. Liver disease induces a complicated imbalance between pro- and antihemostatic elements, thrombocytopenia just being one of them. The mechanism of thrombocytopenia is multifactorial

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© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, © 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

implicating not only sequestration in the spleen, reduction in the mean platelet survival but also decreased platelet production due to low synthesis of thrombopoietin (TPO) [1].

In chronic liver disease, a low platelet count is a marker of severity and is associated with poorer prognosis [2].

Liver transplantation (LT), the main treatment of end-stage liver disease, can also induce decrease of thrombocytes starting intraoperative with the reperfusion syndrome and going on after the procedure due to several mechanisms among which sequestration in the graft plays an important role [1]. Platelets have a dualistic role in LT, both beneficial and detrimental [3].

Thrombocytopenia is defined by platelet count <150,000/mm<sup>3</sup> ; it is mild if platelets are between 75,000 and 150,000/mm<sup>3</sup> , moderate for values between 50,000 and 75,000/mm<sup>3</sup> , and severe if the count is <50,000/mm<sup>3</sup> . Definitions may vary and the limits of platelet count might be different in different studies [4].

substantial and persistent increase in thrombocytes. On the other hand, elimination of the

Bone marrow suppression (HCV, alcohol)

Chronic low-grade disseminated intravascular coagulation

Shunt procedures done either surgically or percutaneously [transjugular intrahepatic portosystemic shunt (TIPS)] are intended at decreasing portal hypertension and hypersplenism might also have a beneficial effect on platelet count. Massoud, following 92 patients that had a TIPS placement, reported a significant increase in platelet number after the procedure, this increase being more important in patients with more severe thrombocytopenia. But TIPS would not have any effect on TPO, this being a possible reason why in some cases there was

Cirrhotic patients waiting for transplantation are sometimes in need for invasive procedures like liver biopsies, endoscopic variceal ligation, paracentesis, and transjugular intrahepatic portosystemic shunt. There is no absolute threshold of platelet count for performing any of

Thrombocytopenia was also a concern in patients with hepatitis C virus (HCV), who needed antiviral therapy with interferon and had to reduce doses or even stop treatment. Nowadays

TPO is a thrombopoietic hormone produced in the liver by both parenchymal cells and sinusoidal endothelial cells at a constant rate. The blood level of TPO is dependent on the uptake by platelets and megakaryocytes, where it is destroyed so if platelet count decreases, less TPO will be uptake and destroyed and its level will rise. Production of TPO is dependent on liver cell integrity; if that is impaired, production will decrease as in cirrhosis. This explains why with a reduction in platelet number TPO level in liver disease would not be elevated, as production is lower. TPO level is inappropriate to platelet level and as a consequence the bone

Antiplatelet antibodies contribute to the premature destruction of the thrombocytes. It was shown among patients with liver disease that up to 64% irrespective of the etiology have platelet-associated anti-glycoprotein (anti-GP) antibodies that are directed against the GP IIb-IX complex. The serum of those patients also has higher levels of platelet-associated immunoglobulin G also implicated in the immune-mediated destruction of platelets [2].

, the risk of bleeding seems to be higher [4].

Thrombocytopenia in Liver Transplant http://dx.doi.org/10.5772/intechopen.72510 87

spleen increases the risk of septic complications and portal thrombosis [4].

Medication

Bleeding

Sequestration Congestive spleen due to portal hypertension

with the new antiviral therapies, this should not be a problem anymore.

marrow stimulation to produce thrombocytes would not be adequate [2, 4].

no effect on platelet number [7].

**Mechanisms**

those procedures but if platelets are <75,000/mm<sup>3</sup>

Altered production Low TPO levels

Enhanced destruction/loss Platelet antibodies

**Table 1.** Causes for thrombocytopenia in chronic liver disease.

The incidence of decreased platelets in chronic liver disease is as high as 76% but moderate in only 13% and severe in 1% of cirrhotic patients [5]. The degree of thrombocytopenia is dependent on the stage of cirrhosis. However, spontaneous bleeding does not occur unless the values reaches 10,000–20,000/mm<sup>3</sup> . There is a difference if an invasive procedure such as liver biopsy, variceal ligation, paracentesis, or major surgery is intended; platelet threshold levels are higher and differ depending on the invasiveness of the maneuver. However, bleeding is not the only concern with thrombocytopenia as platelets have other roles in inflammation, angiogenesis, antimicrobial defense and, of specific importance, in ischemia/reperfusion injury and a beneficial role in liver regeneration [6].
