Inherited bleeding disorders eg haemophilia, VWD, factor deficienciesers Flashcards
Presentations perinatal if inherited bleeding disorder
Prolonged umbilical stump bleed, subdural haematoma
Childhood presentation inherited blood disorder
NAI easy brusing
Polonged APTT
Adulthood inherited bleeding disorder presentation
Menorrhagia, bleeding tendency, prolonged APTT eg IDA, trigger
Coagulation factor disorders
Haemophilia A/B
VWD
Rare eg FVII, FVIII
Bleeding questions to ask in hisotry - ISTH BAT
Epistaxis spontaneously
Large bleeds from small wounds
Gum bleeding
Spontaneous brusiig, size
Bleeding after dental work
Heavy periods
PPI
Musc;e haematoma, haemoarthrosis
intraranial bleeds
Post partm haemorrhage
GI bleeding
Score for bleeding
ISTH BAT
What score in ISTH BAT investigate in
<3 in children
<4 in adult males
<6 in adult females
Investiagtions for inherited bleeding disorders
PT
APTT
Fibrinogen
If abnormal clotting screen with no bleeding history
Factor XII deficiency - confirm with factor assays and reassure
What factor assays do if prolonged PT
Factor VII assay
What factor assays do if prolonged APTT
Factor XII, XI, IX, VIII (12,11,9,8)
What test for if FH od bleeding eg heacy periods
Sus VWD - vWF
Factor VIII - often low as absence of vWF reduces hafl life
How test for vWF
Antigen test - how much
aCTIVITY TEST - how well vWF functions
Blood results in haemophilai
Prolonged APTT - intrinsic. Nomral PT
Decreased VIII (A), IX (B)
Inheritance of haemophilia
X linked
Maternal lines but only sons affected
1 in 3 spontaneous mutations
Clnical features haemophilia
Mostly male
Female if x inactive or compund heterozygotes
Joint bleeding #Porlonged wound and surgical bleeding
What is severe haemophilia A
<1% factor VIII
Features of severe haemophilia A
Early onset - befroe 2 years old
Spontaneous haemarthroses
Moderate haemophilia A factor VIII levels and presentation
1-5%
Late onset
Bleed w trauma or surgery
Mild haemophilia factor VIII levels and features
Few or no bleeds, undetected until later in life
<5% factor VIII
Treating haemophilia
Replace joints if damaged, treat bleeds
Education and self care
Regular prophylaxis
Gene therapy cures
Where is vWF made
Endothelial cells and megakaryocytes
Inheritance of VWD
Autosomal dominant
Midl bleeding disorder
Clinical features VWD
Mucosal bleeding - epistaxis, menorrhagia
GI bleeds
PP bleeding
Post surgical bleedings
Treatment for VWD
Avoid aspirin, anti-inflam or anticoagulant meds
Avoid activities risky for bleeding
vWF role
Mediating platelet adhesion to sites of damaged vascular endothelium
As a bridging molecule for platelet aggregation.
Indirectly it acts as a carrier for FVIII in its inactive form.
Factor VIII works by interacting with factor IX and the intrinsic pathway.
First line in vWD
Desmopressin
What should be tested before demopressin commences
A trial should be carried out with VWF antigen, activity and FVIII measured at baseline, 30-60 mins and 4-6 h
Treatment of bleeding episodes in vWD
1st line - tranexamic acid and desmopressin
2nd - VWF-FVIII concentrate
What is type I VWD
Normal VWF but low levels, also may have low FVIII
AD inheritance, most common form, mild mucatneous unless severe
Menorrhagie, epistacis and brusing
Non O blood gorups have higher VWF levels than O
What is type 2 VWD incl A,B,M,N subtypes
Nomral levels VWF but functionally defective
A - VWF multimers not right size
2B - not right size and too active -> shortage of VWF + platelets
2M - low or absent bindin to platelet receptor.
2N - VWF reduced affinity for factor VIII -> reduced levels.
Which VWD types are autosomal recessive
Type 2N
Type 3 (complete deficiency of VWF)
Casues of acquire VW syndrome - AVWS
> 40 years no prior bleeding history
Lymphoproliferative disease
Myeloproliferative disease
Malignancy - aberrant binding VWF tumour cells
Shear induced VWF conformational changes eg aortic stenosis, ventricular septal defect
AI conditions
Type 3 features clinical VWD
Haemoarthrosis
GI bleeding
What levels of VWD antigen are diagnostic w bleeding history
<0.3
Undetectable = type 3
VWF activity levels -> which tyoe
> 0.6 - type I
<0.6 - type II
Measures risocetintin cofacotr and collagen binding against VWF antigen
Genes responsible for haeophilia
F8 fro A, F9 for B
What is haemophila C
Rosentahl syndrome
Autosmal recessive lack of factor XI
Ashkenazi jeiwsh popylations
What do haemarthroses present with
Painful, erythemaotus, stiff and swollen joint in knees, ankles,elbows
What need to beware of w haemotomas
Compartment syndrome
Should haemophilia cause correction in mixing studies
Yes
Specific clotting factor deficiency
APTT will not correct in acquired haemophilia due to clotting factor antibodies.
Imaging for bleeds
Ultrasound: Useful diagnostic tool for localising site of haemorrhage
Joint X-ray: Can assess ongoing localised damage.
CT/MRI: Excellent at identifying haematomas and haemorrhages such as intracranial bleeding or an iliopsoas haematoma
What type is factor inhibitors more likely in
Haemophiilia A
What disease is given prophylaxis coagulation factors
Severe haemophilia
GOal of prophylaxis with coag factors
30-50% of normal
How give prophylaxis in haemophilia
1-3 infusions a weekminimum of 45 weeks a year
ADjunctive treatment in haemphilia
Fibrinolytic inhibitors - alpha mainocarprioc acid, tranexamic acid
Fibrin glue
Topical thrombin
Complications of haemophilia
Compartment syndrome - haematomas
Arthropathy - haemarthois
Severe haemorrhage - IC, GI
Inhibitor formation requiring higher doses of factor replacement + risk of anaphylaxis
Would mixed studies correct APTT in haemophilia
Yes - factor depletion corrected
Not in acquired as factor antibodies present
Which haemophilia are facotr antibodies more common in
A
Require higher doses of coag factors
Treatment frequency for haemophilia
1-3 transfusions a week
30-50% CGF goal
What meds avoid in haemophilia
NSAIDs and aspirins - increase bleed risk
Complications of haemophilia
Compartment syndrome form haematomas muscle
Arthropathy from haemarthrosis
Sev haemorrhage - GI, intracranial
What is most common nherited bleed disorder
Von willebrands
