Acquired bleeding disorders

Acquired haemophilia A

Acquired haemophilia A is caused by factor VIII autoantibodies which inhibit the activity or increase clearance of factor VIII levels. About half the cases are idiopathic, the others may be associated with the post-partum state, autoimmune or connective tissue disorders, medications and malignancies.

Acquired von Willebrand Disease

Acquired von Willebrand disease is caused by autoantibodies directed against von Willebrand factor (vWF) which results in decreased levels of vWF activity and antigen. Many cases are idiopathic and some are related to monoclonal gammopathy of uncertain significance and lymphoproliferative disorders.

Similar conditions resulting in reduced vWF but due to non-immune causes are grouped as acquired von Willebrand syndrome. Examples include:  

• Shear-induced breakdown e.g aortic stenosis or extracorporeal membrane oxygenation (ECMO)
• Adsorption onto cells or proteins like in some myeloproliferative disorders. 

Liver disease 

Patients may present with a complex bleeding disorder which is often recognised by prolonged PT, APTT and an elevated INR. Liver disease may present a mixture of deficiencies in both procoagulant factors (i.e clotting factors I,II,VII,IX,X) and anti-coagulant factors (protein C, protein S and antithrombin) due to decreased synthesis. Additionally, thrombocytopenia can occur due to hypersplenism, decreased platelet production and increased consumption, Fibrinolysis and DIC can occur in patients with severe cirrhosis.

Use of fresh frozen plasma, cryoprecipitate or platelets may be appropriate in the presence of bleeding and abnormal coagulation. Vitamin K may have a role.

Vitamin K deficiency

Vitamin K deficiency can lead to reduced activity of vitamin K dependent clotting factors II, VII, IX, X and protein C and protein S; often with prolongation of the PT and APTT.  Risk factors for vitamin K deficiency include poor diet, malabsorption, antibiotic use, and liver or kidney dysfunction. Treatment is vitamin K given orally, subcutaneously or intravenously, depending on the clinical circumstances. Rarely, prothrombin complex concentrate (PCC) may have a role.

Uraemia

Patients with uraemia develop a mild to moderate haemostatic defect due to platelet dysfunction, abnormalities of vWF multimers and decreased platelet vWF. Anaemia with decreased haematocrit further aggravates in vivo platelet dysfunction due to reduction of platelet interaction with endothelial cells. The levels of clotting factors are usually normal, and elevated levels of fibrinogen, factor VIII and vWF may occur.

Haemostatic management is based on clinical bleeding risk. Platelet  transfusion may be helpful in an acute life-threatening bleed however the transfused platelets rapidly become dysfunctional in the uraemic environment. Dialysis usually improves platelet dysfunction but incompletely corrects the haemostatic defect.  Desmopressin (DDAVP) provides some short-term improvement of haemostasis with maximal effect at 4 hours which wears off by 6–8 hours in many patients. Repeated administration of DDAVP may lead to tachyphylaxis and hyponatremia.

Cardiopulmonary bypass (CPB) 

The cause of the haemostatic defect with CBP is multifactorial involving decreased coagulation factor levels due to activation from contact with the extracorporeal circuit and oxygenator; thrombocytopenia with platelet dysfunction; fibrinolytic activation and haemodilution.

Transfusion of platelets or fresh frozen plasma may be appropriate in the presence of major haemorrhage and abnormal coagulation. In this situation, due to platelet dysfunction, the platelet count is not a reliable indicator of bleeding risk.

Disseminated intravascular coagulation (DIC)

DIC results from inappropriate and excessive systemic activation of the coagulation system with poorly regulated local or systemic thrombin generation. This leads to fibrin deposition in both small and large vessels. Concurrently consumption of coagulation factors and platelets may occur and lead to bleeding. Levels of inhibitors of coagulation such as Antithrombin, Protein C and Protein S may be reduced aggravating thrombin formation. Patients with DIC may have simultaneous bleeding and thrombosis.

Common causes of DIC include sepsis; malignancy e.g. acute promyelocytic leukaemia, pancreatic cancer and ovarian cancer; trauma; obstetrics complications e.g. preeclampsia, abruptio placentae, fetal death in utero; and acute haemolytic transfusion reaction in the setting of ABO-incompatible blood transfusion.

Acute DIC is a medical emergency and therapy is always aimed towards eliminating the precipitating trigger. In the presence of widespread bleeding, specific replacement with blood component therapy should be given and subsequent transfusion guided by repeated blood tests.

Cryoprecipitate, FFP and platelets may be required in patients with serious bleeding. The role of heparin is controversial. 

Updated September 2025