Failing to correct thrombocytopenia prophylactically to decrease the risk of procedure-related bleeding
There are several factors that can cause thrombocytopenia in patients who have chronic liver disease. Those factors most frequently involved in determining severe thrombocytopenia—commonly defined as a platelet count below 50x109/L—are splenic sequestration of platelets due to portal hypertension and decreased thrombopoietin synthesis in a failing liver.32 Despite a low platelet count being a fairly frequent finding in patients who have cirrhosis, severe thrombocytopenia is observed in ≤1% of patients, normally those with more advanced stages of liver disease, such as Child-Pugh class C patients.33 Besides a reduction in platelet number, there is evidence of altered platelet function in patients with liver disease. However, it needs to be emphasized that whether there is a clear functional platelet defect in terms of hypoaggregability is debated, and the evidence supporting this finding is controversial, mainly because the in vitro studies that have explored this issue lacked standardization (e.g. not under flow conditions, using adjusted platelet count, etc.).34
In patients with liver disease, the most clinically-evident platelet alteration, that is a decrease in their number, is a slow and progressive process and increased von Willebrand Factor (vWF) levels tend to compensate for thrombocytopenia.35 In more detail, endothelial perturbation and both reduced activity and levels of the cleaving protease ADAMTS13 are responsible for elevated vWF levels in patients with cirrhosis, and there is compelling evidence that this phenomenon supports adequate platelet adhesion despite their reduced numbers.35 In addition, this finding may also be responsible for the apparently paradoxical prothrombotic tendency that can be observed in severely thrombocytopenic patients with cirrhosis under some conditions, such as systemic inflammation, when further reduced ADAMTS13 activity may tip the coagulation balance towards a prothrombotic state.36
This complex picture should be framed in the clinical context of a patient with advanced liver disease who needs an invasive procedure, where platelet transfusion is often recommended due to the perceived risk of procedure-associated bleeding secondary to thrombocytopenia. Overall, the aforementioned findings support this notion, further backed by practical evidence, that significant bleeding as a consequence of an invasive procedure is a rare event in patients with cirrhosis. In fact, some common clinical procedures in patients with advanced liver disease, such as paracentesis or thoracentesis, do not require platelet transfusion even in patients with severe thrombocytopenia, as there is evidence of a lack of increased bleeding risk in these patients unless there is an inadvertent vessel puncture.
These suggestions are reinforced by a study that included a large series of paracenteses (n=1,100) carried out by trained nurses, where 54.4% of patients had severe thrombocytopenia, and where no bleeding episodes occurred even in the absence of prophylactic platelet transfusion.23 Furthermore, in a series of 9,320 thoracenteses the rate of bleeding complications was 0.18%, with no bleeding episodes observed in patients who had a platelet count below 50x109/L.37 Lastly, other procedures frequently carried out in patients with cirrhosis, such as dental extractions or prophylactic oesophageal banding ligation, have a low incidence of significant bleeding complications—2.9% and approximately 5%, respectively—that are unrelated to platelet count.24,38,39 Furthermore, in the only prospective study in which dental extractions were performed without administration of blood products and where 34.4% of the procedures were performed in patients with platelet counts of 30–50x109/L, application of local pressure with a gauze achieved adequate haemostasis.24 Moreover, bleeding following oesophageal banding ligation has often been described as a late event associated with banding dislodgment.38,39
However, there are some clinical procedures—such as liver biopsy or ablation of liver tumours—where bleeding seems more closely associated with severe thrombocytopenia. Indeed, there is a reported thrombocytopenia incidence of 5.3% following liver biopsy in patients with platelet counts of 50–60x109/L, and of 0.8% in those with platelet counts >60x109/L, while in patients undergoing percutaneous ablation of hepatocellular carcinoma a platelet count <50x109/L increased the risk of bleeding by nearly ninefold.40,41
What are the concrete implications that can be gathered from this evidence and that may help us avoid pitfalls when managing these patients in clinical practice? The 50x109/L platelet count limit is still considered the ‘magic threshold’ below which even experts in coagulation in liver disease and society recommendations agree that platelet counts should be raised, either by platelet transfusion or by means of thrombopoietin receptor agonists, in order to decrease the likelihood of bleeding in the case of high-risk procedures.6,42–44 The results of pragmatic studies designed to identify whether proactively increasing platelet counts, by any means, before a procedure might be associated with an actual decrease in the risk of bleeding, compared with a reactive, wait-and-see strategy that involves blood product administration only in the case of bleeding, are eagerly awaited. In the meantime, the recommendation to maintain a platelet count above 50x109/L in patients undergoing high-risk, or even low-risk, procedures still holds true if the occurrence of bleeding may be catastrophic (e.g. intracranial) or cannot be easily managed by local haemostasis.
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