Acquired haemophilia A
Acquired haemophilia A is caused by neutralising factor VIII autoantibodies which decrease FVIII levels. About half the cases are idiopathic, the others may be associated with the post-partum state, connective tissue disorders 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, lymphoproliferative disorders and myeloproliferative disorders.
Patients may present with a complex bleeding disorder which is often recognised by an elevated INR. Liver disease may present a mixture of both pro and anti-coagulant factor deficiency due to decreased synthesis, thrombocytopenia due to hypersplenism, decreased production and increased consumption, platelet dysfunction, anaemia, fibrinolysis and sometimes DIC.
Vitamin K deficiency
Vitamin K deficiency can lead to reduced activity of 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. Occasionally Prothrombinex®-VF or FFP may have a role.
Patients with uraemia develop a mild to moderate haemostatic defect due to platelet dysfunction, abnormalities of vWF multimers and decreased platelet vWF. A decreased haematocrit further aggravates in vivo platelet dysfunction. 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 emergencies however the infused platelets rapidly become dysfunctional in the uraemic environment. Dialysis usually improves platelet dysfunction but incompletely corrects the haemostatic defect. Red cell transfusion to is used to achieve a haematocrit >27%. 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. Cryoprecipitate often promptly shortens the bleeding time and decreases bleeding.
Thrombolytic drugs can cause systemic fibrinolysis. Haemorrhage complicating these agents is most commonly localised (e.g. at the site of catheterisation in the groin). Therefore, control localised bleeding with pressure packs. Cryoprecipitate or fresh frozen plasma can be given for life-threatening bleeding.
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.
Management of haemorrhage includes rapid control of the source of bleeding and restoration of circulating blood volume to correct hypoperfusion to end organs. Uncontrolled blood loss also contributes to the development of haemostasis failure which further exacerbates bleeding.
Restoration of circulating volume is initially achieved by rapid infusion of crystalloid or colloid. Clinical trials in humans have not demonstrated that albumin solutions or other colloids are superior to crystalloid in resuscitation, but larger quantities of crystalloid are required.
Red cells are necessary for their oxygen carrying capacity and also contribute to improving haemostasis. The need for red cell transfusion depends on the estimated loss of circulating blood volume, and the patient’s ability to compensate for the quantity of blood lost.
Blood volume can be estimated as approximately 70 mL/kg for adults, 80 mL/kg in children and 100 mL/kg in neonates.
Red cell transfusion is usually required when 30–40% of blood volume is lost (1,500 mL in a 70 kg male) and more than 40% blood volume loss (1,500 to 2,000 mL) is life- threatening and requires immediate transfusion.
Obstetric haemorrhage is predominantly postpartum, representing 80% of cases. Worldwide, massive obstetric haemorrhage, resulting from the failure of normal obstetrical, surgical and/or systemic haemostasis, is responsible for 25% of the estimated 358,000 maternal deaths each year. In Australia, it complicates 3-6% of pregnancy.
Blood loss can be notoriously difficult to assess in obstetric bleeds. Bleeding may sometimes be concealed and the presence of amniotic fluid makes accurate estimation challenging. Post-partum haemorrhage (PPH) has been defined as a blood loss of 500 mL or more during puerperium and severe PPH as a blood loss of 1,000 mL or more.
Goals in the management of transfusion in severe haemorrhage include: Rapid resuscitation with crystalloids to restore and maintain the circulating blood volume; maintenance of tissue oxygenation using group specific or O negative and Kell negative red blood cells; and reversal or prevention of coagulopathy using appropriate blood and plasma components. Visco-elastic tests such as TEG and ROTEM may be useful in guiding therapy. Local or national guidelines should be followed for the dose and timing of blood component administration.
Additional guidelines on the appropriate use of blood products as well as methods to minimise blood loss are also discussed in The Royal College of Obstetrics and Gynaecologists guideline and Patient Blood Management Guideline: Module 5.
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 heamolytic 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 is a source of fibrinogen and may be required. Prothrombinex-VF is generally contraindicated as it may potentiate existing thrombotic tendency, which is a feature of patients with DIC. The role of heparin is controversial. Antithrombin (Thrombotrol-VF) replacement may have a role in the management of those patients who do not respond to simple replacement therapy of blood components and consultation with a specialist is recommended.