Bleeding Disorders (including thrombocytopenia) Flashcards
What is thrombocytopenia?
Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L. There are a long list of causes of a low platelet count. They can be split into problems with production or destruction.
problems with production
Sepsis B12 or folic acid deficiency Liver failure causing reduced thrombopoietin production in the liver Leukaemia Myelodysplastic syndrome
Problems with destruction
Medications (sodium valproate, methotrexate, isotretinoin, antihistamines, proton pump inhibitors) Alcohol Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Heparin induced thrombocytopenia Haemolytic-uraemic syndrome
Presentation
A mild thrombocytopenia may be asymptomatic and found incidentally on a full blood count.
Platelet counts below 50 x 109/L will result in easy or spontaneous bruising and prolonged bleeding times. They may present with nosebleeds, bleeding gums, heavy periods, easy bruising or blood in the urine or stools.
Platelet counts below 10 x 109/L are high risk for spontaneous bleeding. Spontaneous intracranial haemorrhage or GI bleeds are particularly concerning.
DDx of abnormal or prolonged bleeding
Thrombocytopenia (low platelets)
Haemophilia A and haemophilia B
Von Willebrand Disease
Disseminated intravascular coagulation (usually secondary to sepsis)
What is immune thrombocytopenia purpura
ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.
How to manage immune thrombocytopenia purpura?
Prednisolone (steroids)
IV immunoglobulins
Rituximab (a monoclonal antibody against B cells)
Splenectomy
The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help. Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.
What is thrombotic thrombocytopenia purpura?
This is a condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.
Why do blood clots develop in thrombotic thrombocytopenia purpura?
The blood clots develop due to a problem with a specific protein called ADAMTS13. This protein normally inactivates von Willebrand factor and reduces platelet adhesion to vessel walls and clot formation. A shortage in this protein leads to von Willebrand factor overactivity and the formation of blood clots in small vessels. This causes platelets to be used up leading to thrombocytopenia. The blood clots in the small vessels break up red blood cells, leading to haemolytic anaemia.
What can ADAMTS13 protein deficiency be due to
due to an inherited genetic mutation or due to autoimmune disease where antibodies are created against the protein.
treatment for thrombotic thrombocytopenia purpura?
plasma exchange, steroids and rituximab (a monoclonal antibody against B cells).
What is heparin induced thrombocytopenia?
Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin. These heparin induced antibodies specifically target a protein on the platelets called platelet factor 4 (PF4). These are anti-PF4/heparin antibodies.
What causes heparin induced thrombocytopenia?
The HIT antibodies bind to platelets and activate clotting mechanisms. This causes a hypercoagulable state and leads to thrombosis. They also break down platelets and cause thrombocytopenia. Therefore there is an unintuitive situation where a patient on heparin with low platelets forms unexpected blood clots.
HOw to test for heparin induced thrombocytopenia?
Diagnosis is by testing for the HIT antibodies in the patients blood.
How to manage heparin induced thrombocytopenia?
Management is by stopping heparin and using an alternative anticoagulant guided by a specialist.
VWD- What is von willebrand disease?
most common inherited cause of abnormal bleeding (haemophilia). There are many different underlying genetic causes, most of which are autosomal dominant. The causes involve a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF). There are three types based on the underlying cause and ranging from type 1 to type 3. Type 3 is the most severe.
VWD- presentation
Patients present with a history of unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Nose bleeds (epistaxis)
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during surgical operations
Family history of heavy bleeding or von Willebrand disease is very relevant.
VWD- diagnosis
Diagnosis is based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations. Due to all the underlying causes there is no easy von Willebrand disease test. This can make diagnosis challenging and beyond the scope of most medical exams.
VWD - management
Von Willebrand disease does not require day to day treatment. Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):
Desmopressin can be used to stimulates the release of VWF
VWF can be infused
Factor VIII is often infused along with plasma derived VWF
Women with VWD that suffer with heavy periods can be managed by a combination of:
Tranexamic acid Mefanamic acid Norethisterone Combined oral contraceptive pill Mirena coil Hysterectomy may be required in severe cases
H- what causes haemophilia a?
Haemophilia A is caused by a deficiency in factor VIII
H- what causes haemophilia b?
Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.
H- what are haemophilia a and b genetically?
Both haemophilia A and B are X linked recessive. This means in order to have the condition all of the X chromosomes need to have the abnormal gene
almost exclusively affect males.
H- S+S
Patients can bleed excessively in response to minor trauma and are also at risk of spontaneous haemorrhage without any trauma.
Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates.
Spontaneous bleeding into joints (haemoathrosis) and muscles are a classic feature of severe haemophilia and worth remembering for your exams. If untreated this can lead to joint damage and deformity.
H- Where can abnormal bleeding also occur (less characteristic)?
Gums Gastrointestinal tract Urinary tract causing haematuria Retroperitoneal space Intracranial Following procedures
H- diagnosis
bleeding scores, coagulation factor assays and genetic testing.
H- management
The affected clotting factors (VIII or IX) can be replaced by intravenous infusions. This can be either prophylactically or in response to bleeding. A complication of this treatment is formation of antibodies against the clotting factor resulting in the treatment becoming ineffective.
Acute episodes of bleeding or prevention of excessive bleeding during surgical procedures involve:
Infusions of the affected factor (VIII or IX)
Desmopressin to stimulate the release of von Willebrand Factor
Antifibrinolytics such as tranexamic acid
