Lessons From the Liver: Rebalanced Hemostasis in Immune Thrombocytopenia

Common laboratory tests of the hemostatic system, such as the platelet count, activated partial thromboplastin time (aPTT), and prothrombin time (PT), are often abnormal in patients with liver disease. If interpreted in isolation, these laboratory abnormalities appear to indicate a tendency for the patient to bleed. Consequently, clinicians often transfuse blood products in an attempt to normalize these laboratory abnormalities, especially before invasive procedures. In recent years, there has been an increasing understanding of a “rebalancing” of the hemostatic system in liver disease, whereby hemostatic changes that promote bleeding can be counterbalanced by hemostatic changes that promote thrombosis.¹  Thus, the platelet count, aPTT, and PT, although commonly ordered, fail to reflect the globally rebalanced hemostasis of liver disease, which can lead to unnecessary and possibly harmful treatments. Indeed, preoperative “correction” of these laboratory abnormalities does not necessarily reduce bleeding and may actually promote it.

Immune thrombocytopenia (ITP) is another disorder in which a laboratory abnormality (i.e., the platelet count) does not accurately predict the risk of bleeding, especially for the individual patient. A singular focus on the platelet count in ITP can cause a clinician to make the treatment for ITP worse than the disease itself, especially for childhood ITP. Such unnecessary therapy and resulting iatrogenic morbidity has been called “medical nemesis.”²  To decrease medical nemesis in ITP, it is important to begin to understand why some patients do not bleed despite severe thrombocytopenia and why severe hemorrhage can occur despite treatment to raise the platelet count. One possible explanation could be that there are hemostatic differences beyond the platelet count that predispose to severe bleeding.

Dr. Won Ho Kim and colleagues from Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, sought evidence for a rebalancing of hemostasis in ITP, similar to that proposed for liver disease, which could explain the frequent disconnect between the platelet count and the occurrence of bleeding. They built upon prior observations that a global assessment of hemostasis (thromboelastography) might predict bleeding in ITP³  and that the reported decrease in von Willebrand factor (vWF) cleaving protease activity in ITP⁴  could conceivably mitigate the effects of thrombocytopenia. Dr. Kim and colleagues measured vWF antigen levels and performed rotational thromboelastography in 20 adults with ITP and followed them for six months for the occurrence of bleeding. The mean vWF antigen level was 163 percent (S.D. 80%), and eight patients (40%) had elevated vWF antigen levels (218%, S.D. 104%) when adjusted for their blood group type. Thromboelastography parameters were within the normal range for most patients. A subgroup analysis compared patients with normal versus elevated vWF. Those with elevated vWF were older and had longer duration of ITP. The clot formation time (CFT) was shorter, and the α-angle was larger in those with elevated vWF. The CFT and α-angle are sensitive to platelet number and function and fibrinogen level and polymerization. So, higher vWF levels were associated with better thromboelastography values compared with lower vWF values despite a similar platelet count. Severe bleeding did not occur in any patient, but four patients had minor bleeding (3 in the normal vWF group).