BLEEDING DISORDERS AND THROMBOSIS Flashcards
In a patient with a bleeding disorder where the mucous membranes are most affected, what is the likely underlying pathology?
Platelet defects
Von Willebrand disease
In a patient with a bleeding disorder where the bleeding happens into joint and muscles, what is the likely underlying pathology?
Coagulation factor deficiencies
What are the common features of a history of someone with a bleeding disorder?
Prolonged epistaxis (nosebleed)
Cutaneous haemorrhage or bruising with minimal or no trauma
Prolonged bleeding from trivial wounds
Oral cavity bleeding
Spontaneous gastrointestinal bleeding
Menorrhagia not associated with structural lesions of the uterus
What are the common acquired causes of a coagulopathy?
Vitamin K deficiency
Disseminated Intravascular Coagulation (DIC)
Liver disease
What are the screening tests and first line investigation that should be ordered for someone with a suspected bleeding disorder?
Full blood count Prothrombin time Activated partial thromboplastin time Thrombin time or fibrinogen PFA 100 closure or bleeding time
Factor VIII and von Willebrand (VWF) factor activity
VWF antigen
Platelet aggregation
Platelet nucleotides
What are the second line investigations that should be ordered in someone with a suspected bleeding disorder where the first line investigations came back negative?
Factor XIII
α2-antiplasmin
In the coagulation cascade, what is the purpose of factor VIII?
When converted into VIIIa, it enables the conversion of factor X into Xa. IXa must also be present for this to happen.
What are the two pathways of the coagulation cascade?
Contact activation (intrinsic) pathway Tissue factor (extrinsic) pathway
What are the factors that make up the intrinsic (contact activation) pathway of the coagulation cascade?
XII - XIIa
XI - XIa
IX - IXa
VIII - VIIIa
What are the factors that make up the extrinsic (tissue factor) pathway of the coagulation cascade?
VII - VIIa
X - Xa
Tissue factor (III)
What are the factors that make up the common pathway of the coagulation cascade?
II (Prothrombin) IIa (Thrombin) V - Va I (Fibrinogen) Ia (Fibrin) XIII - XIIIa
What does the activated partial thromboplastin time (APTT) represent?
Performance indicator of the efficacy of both the intrinsic (contact activation) pathway and the common coagulation pathway.
What does the prothrombin time (PT) represent?
Measure of the extrinsic pathway of coagulation.
What factor is deficient in haemophilia A?
VIII
What factor is deficient is haemophilia B?
IX
What is the prevalence of haemophilia A among males?
1 in 5000
What is the prevalence of haemophilia B among males?
1 in 25000
Below what percentage of factor VIII or IX are patients considered to have severe haemophilia?
Less than 1%
Within what range, as a percentage of factor VIII or IX, are patients considered to have moderate haemophilia?
1-5%
Above what percentage of factor VIII or IX are patients considered to have mild haemophilia?
> 5%
What is the standard treatment for patients with mild haemophilia A?
Desmopressin or clotting factors
What is the treatment for patients with moderate or severe haemophilia A?
Clotting factor VIII injections
What commonly used drugs must those with bleeding disorders avoid?
NSAIDs and aspirin
What is another term for haemophilia B?
Christmas disease
What is the role of von Willebrand factor?
Promoting platelet adhesion to exposed collagen
Protects factor VIII in the circulation
What are the clinical features of von Willebrand disease?
Mucocutaneous bleeding as a result of abnormal platelet function.
Menorrhagia is common.
What is the pattern of inheritance of von Willebrand disease?
Autosomal dominant
How is von Willebrand disease treated?
Desmopressin
Clotting factors
What are the three common acquired bleeding disorders?
Vitamin K deficiency
Liver disease
Disseminated intravascular coagulation
What is disseminated intravascular coagulation?
A process characterised by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body. This leads to compromise of tissue blood flow and can ultimately lead to multiple organ damage. In addition, as the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur from various sites.
Disseminated intravascular coagulation occurs as a complicating factors for other underlying conditions. What conditions can lead to DIC?
Cancer - both solid and blood (particularly acute promyelocytic leukemia)
Obstetric complications - eg pre-eclampsia
Massive tissue injury - eg burns
Sepsis
Transfusion reaction
Severe allergic or toxic reaction - eg snake venom
Large aortic aneurysms
What investigations might be ordered to further assess someone with suspected disseminated intravascular coagulation? For each state what might be found in a positive result.
Prothrombin time increase Activated partial thromboplastin time increase Low fibrinogen Rapidly declining platelet count Positive D-dimer Blood film shows schistocytes
How is disseminated intravascular coagulation treated?
Transfusion of fresh frozen plasma and platelets
Heparin is not used due to the risk of bleeding
How does liver disease lead to a bleeding disorder?
Loss of synthetic function which results in reduced amounts of proteins used in the coagulation cascade. Coagulopathy usually happens in conjunction with thrombocytopenia.
What is thromobocytopenia?
Low platelet count
How is vitamin K involved in the coagulation cascade?
Vitamin K is involved in the post-translational modification of factors II, VII, IX and X.
It is also involved in activated protein C.
What are the risk factors for venous thromboembolism?
Age Immobilization and paresis Surgery and trauma Malignancy Pregancy and the puerperium (post-delivery) Combined oral contraceptive pill Hormone replacement therapy Inherited thrombophilias Antiphospholid antibodies Raised coagulation factors Family history Serious illness Obesity Varicose veins Smoking
How is the diagnosis of a DVT or PE excluded?
Ultrasound
D-dimer
What are the inherited thrombophilias?
Antithrombin deficiency Protein C deficiency Protein S deficiency FV Leiden Increased levels of prothrombin (G20210A)
How does antithrombin work?
Most of the coagulation proteins are serine proteases. Antithrombin is a serine protease inhibitor. It works mainly to neutralise thrombin (factor II), but it also has some effect on Xa.
How do proteins C and S work as natural anticoagulants?
Activated protein C cleaves the two co-factors in the intrinsic coagulation pathway (V and VIII). Protein S is the cofactor to protein C. They are both vitamin K dependent proteins.
How is protein C activated as a natural anticoagulant?
It is activated by thrombin in the presence of an endothelial cofactor, thrombomodulin.
Are heterozygotes of antithrombin, protein C or protein S deficiency affected?
Yes, they have 50% of the levels and are therefore at risk. Therefore it is considered autosomal dominant.
What is FV Leiden disease?
This is a disease where there is resistance to protein C, a natural anticoagulant. It is as result of a mutation in the gene for factor V.
What is the prevalence of FV Leiden disease among DVT patients?
20%
How are venous thrombolembolisms treated?
Anticoagulation with heparin (SC, OD) followed by warfarin for 6 months if there has been no identified cause or lifelong if this is a recurring DVT/PE. Target INR is 2-3.
