Bleeding Disorders Flashcards
What are the top differentials for abnormal bleeding?
Thrombocytopenia,
von Willebrand disease,
Haemophillia A or B,
DIC
What are the causes of severe thrombocytopenia
ITP,
DIC,
TTP,
Haemtological malignancy
What are causes of moderate thrombocytopenia?
Heparin induced thrombocytopenia,
Drug-induced,
Alcohol,
Liver disease,
Hypersplenism,
Viral infections,
Pregnancy,
SLE,
Vitamin B12
What are causes of thrombocytopenia associated with reduced platelet production?
Viral infections eg, EBV, CMV and HIV.
B12 deficiency
Folic acid deficiency,
Liver failure causing reduced thrombopoietin,
Leukaemia,
Myelodysplastic syndrome,
Chemotherapy
What are causes of thrombocytopenia associated with increased platelet destruction?
Medications eg, sodium valproate, methotrexate.
Alcohol,
Immune thrombocytopenic purpura,
Thrombotic thrombocytopenic purpura,
Heparin induced thrombocytopenia,
Haemolytic uraemic syndrome
What is the presentation of thrombocytopenia?
Below 50 it may present with nose bleeds, bleeding gums, heavy periods, haematuria, rectal bleeding.
Below 10 it can present with intracranial haemorrhage and GI bleeding
What is immune thrombocytopenic purpura?
Autoimmune disease where antibodies are targeted against the platelets.
Presents with non-blanching purpura.
What is the management of ITP?
Prednisolone,
IV immunoglobulins,
Thrombopoietin receptor agonists,
Rituximab,
Splenectomy
What is thrombotic thrombocytopenic purpura?
Tiny thombi form in vessels which causes microangiopathy. Caused inherited by defect in ADAMTS14 protein or antibodies are created against the protein. Diagnosis by looking at ADAMTS13 activity.
What is the normal function of the ADAMTS13 protein?
inactivates von willebrand factor,
Reduces platelet adhesion to vessel walls,
Reduces clot formation
What is the presentation of TTP?
Pentad to remember:
Fever,
Microagiopathic haemolytic anaemia,
Thrombocytopenic purpura,
CNS involvement (headaches, confusion, seizures)
AKI
What is the management of TTP?
FFP,
Plasma exchange,
High dose steroids, low dose aspirin and rituximab.
Describe features of heparin induced thrombocytopenia
Development of antibodies against platelets in response to heparin. This triggers clotting and so you get thrombosis. Think when patient is on heparin and clotting!!
Diagnosis - HIT antibodies.
Treatment - Stop heparin and use alternative
What is von Willebrand disease and the different types
Autosomal dominant condition where there is defect in VWF (exposed when endothelial damage, causes platelets to bind and aggregate)
Type 1 - Partial deficiency of VWF (mildest and most common)
Type 2 - Reduced function of VWF.
Type 3 - Complete deficiency of VWF (most severe but rare type)
Explain the extrinsic pathway of secondary haemostasis (initiation of the coagulation cascade)
Tissue factor binds to factor VII (7) activating it. Activated factor VII causes the activation of factor X (10). Activated factor 10 causes the activation factor V (5) which forms a complex with activated factor 10 and factor II (2 also known as prothombim) to form a prothombinase complex which causes the activation of factor 2 (prothombin to thrombin)
Factor IIa will go onto to activate fibrinogen into fibrin and factor XIII. Factor XIII then can cross link the fibrin which makes it stronger
Explain the intrinsic pathway (propagation of the coagulation cascade)
The extrinsic pathway makes a small amount of thrombin which can go on to activate factor XI and factor VIII. Activated factor XI will activate factor IX. Now activated factors VIII and IX stimulate the prothombinase complex resulting in the formation of more thrombin.
What is the presentation of von willebrand disease?
Nosebleeds,
Bleedign gums when brishing teeth,
Easy bruising,
Menorrhagia
What are the investigations for von willebrand disease?
Prolonged bleeding time.
APTT may be prolonged.
Factor VIII levels reduced (Factor 8 degrades rapidly when not bound to WVF)
Defective platelet aggregation
What is the management of von Willebrand disease?
Desmopressin (stimulates release of VWF from endothelium), This is first line.
Tranexamic acid,
Von Willebrand factor infusion +/- Factor VIII (in the context of heavy bleeding)
For heavy periods - TXA, mefenamic acid, mirena coil, COCP,
Describe general features of haemophilia
Both are X-linked recessive disorders. Haemophilia A is deficiency in factor VIII (more common).
Haemophilia B is caused by a deficiency in factor IX.
What is the presentation of Haemophilia?
Typically presents early in life with spontaneous bleeding into soft tissue, joints and muscle. This can present with haemarthrosis, compartment syndrome, nose bleeds, GI bleeding, haematuria
What is the diagnosis and management of haemophilia?
Diagnosis - Bleeding scores, coagulation factor assays and genetic testing. Prolonged APTT but PT normal and thrombin time normal
Management - Give affected clotting factors as an IV infusion regularly or in response to bleeding. Risk of developing antibodies towards recombinant factors
Avoid TXA in haemarthrosis but can use in bleeding soft tissue wounds
Describe disseminated intravascular coagulation and its causes
It is an acquired disease which causes microthrombi due to activation of the coag cascade and bleeding due to exhaustion of the coag cascade.
Caused by sepsis, malignancy, massive haemorrhage, severe trauma and pregnancy complications (pre-eclampsia, placental abruption, amniotic fluid embolism).
What are the laboratory investigations for DIC?
PT and APTT are both prlonged, Fibrinogen reduced.
D-dimer
FBC, Platelets and blood film which shows RBC fragments (Due to fibrin which lays down in the vessel and cuts the RBCs as they travel past)
