Clotting disorders Flashcards
What tests should be done for coagulations disorders?
FBC (with platelet count)
PT (prothrombin time)
APTT (activated partial thromboplastin time)
Fibrinogen levels
How do you check whether there is a factor deficiency or a coagulation factor inhibitor present?
50/50 mixture study of patient:normal plasma
- If it corrects = deficiency
- If it does NOT correct = inhibitor
e.g. If APTT corrects when mixed with normal plasma it means that there is a coagulation factor deficiency
What factor deficiency causes Haemophilia A?
Factor VIII
What factor deficiency causes Haemophilia B?
Factor IX
What factors are measured in extrinsic pathway?
TF (tissue factor)
VIIa to Xa
PT (prothrombin time)
What is tissue factor’s function in the extrinsic pathway?
TF extruded from damaged endothelial cells of vessel walls activates factor VII to initiate extrinsic system
What factors are measured in the intrinsic pathway?
IX - XII to VIIIa to Xa
APTT
What factors are measured in the common pathway?
Xa -> thrombin
TT and PT, APTT
Often just measure fibrinogen
What differentials may be the cause of a prolonged PT?
Older patients - warfarin
2nd commonest cause - VII deficiency
Also affected by factors: II, V and X
What differentials may be the cause of a prolonged APTT?
Due to patient being on heparin
Also affected by factors: VIII, IX, XI and XII (but XII does NOT cause bleeding)
Von Willebrand’s Disease
If BOTH PT and APTT are prolonged what differentials should be considered?
Vitamin K deficiency + low fibrinogen -> Liver disease, malabsorption
DIC (disseminated intravascular coagulation) + low fibrinogen -> FDPs, D-dimers raised, low platelets, red-cell fragments
Heparin toxicity + normal fibrinogen
Rarely (deficiencies of factor V or X) + normal fibrinogen
What factors are dependent on vitamin K?
Factors II, VII, IX and X
What is the diagnostic triad for clotting disorders?
- Personal history of bleeding
- Family history of bleeding
- Supportive laboratory tests
What is looked for in personal history of bleeding?
- Bruising - in unexpected places, no injury
- Epistaxis (nosebleed) - duration > 30 mins and frequency
- GI tract: start at mouth and work down
- Menses - duration, flooding/clots, no of pads/tampons
- Urine - haematuria
Need to know
• Surgical history
• Dental history (may have been complicated due to bleeding)
• Cuts and injuries
What is looked for in family history of bleeding?
- Known bleeding disorders
- Bleeding in family members especially after surgery or dentistry
- If there is - get details of where tested, by whom and when
What is looked for in diagnostic tests?
FBC - e.g. will show thrombocytopenia (low platelet level)
Microscopy
- Large platelets - Bernard Soulier Syndrome
- Small Platelets - Wiskott Aldrich Syndrome
- Neutrophil inclusions - May Hegglin Anomaly
- Platelet inclusions - Paris Trousseau/Jacobsen’s
PFA - screen of platelet function Coagulation tests: - PT (prothrombin time) - APTT (activated partial thromboplastin time) - TT (thrombin time) - Fibrinogen - 50/50 mixture test
What is vWF disease?
- Endothelial cells are attached to the subendothelial collagen by von Willebrand factor (vWF) which these cells produce
- vWF is also stored in the Weibel-Palade bodies of the endothelial cells and secreted constitutively into the blood. Platelets store vWF in their alpha granules
- vWF carries FVIII in the blood
- The commonest coagulopathy
- Affects 0.5% of population
- Mucocutaneous bleeding
- 15% of menorrhagia
What are the types of von Willebrand’s Disease?
Type 1 - REDUCED amount of normal vW protein
Type 2 - ABNORMAL vW protein (IIb overactive)
Type 3 - LITTLE/NO vW protein
How is von Willebrand’s screened for?
- Factor VIII - normal range: 50-150 iu/dl
- von Willebrand’s Antigen - normal range: 50-150 iu/dl
- von Willebrand activity - normal range: 50-150 iu/dl
How is type 1 and type 2 vW disease differentiated?
By using ratio of vWF activity: vWF antigen
- if ratio of vWF activity to vWF antigen is >0.6 = type 1
- if ratio <0.6 = type 2
How does type 1 vW disease present?
- Mild disease
- Bruising/mucosal bleeding
- Menorrhagia
- Operations - dental extractions
How does type 2 vW disease present?
• Clinically indistinguishable from type 1 • Type 2b: ◦ OVERACTIVE protein ◦ Can result in thrombocytopenia ◦ Avoid DDAVP, use vWF concentrate
How does type 3 vW disease present?
- Severe illness
- Serious mucosal bleeding
- Operative treatment will cause severe bleeding
How is type 1 and type 2 vW disease treated?
DDAVP - release vW protein from storage
- do NOT use in type 2b
Local measures - give iron (due to blood loss)
Use vWF concentrate if needed
