Bleeding Disorders Flashcards
Inherited definition
traits present from birth and genetically derived from parents/ancestors
Acquired definition
traits that develop during a person’s lifetime. Not passed from one generation ot another.
Haemophilia/Bleeding Disorder definition
a problem with the blood clotting process, which can lead to abnormally heavy and prolonged bleeding. The bleeding can even be “spontaneous”
Causes of abnormal bleeding
- blood vessel/vascular disorders
- platelet disorders
- coagulation pathway disorders
Examples of inherited blood vessel/vascular disorders (2):
- hereditary haemorrhagic telangiectasia aka osler weber rendu syndrome
- collagen abnormalities: Ehlers-Danlos
Syndrome
Examples of acquired blood vessel/vascular disorders (3):
- Scurvy (vitamin C deficiency)
- Steroid Rx (Cushing’s syndrome)
- Old age
- common?
- type of mutation
- is
- ## causes (3)
- effect on platelet count
- effect on coagulation screen
- aka Osler-Weber-Rendu syndrome
- uncommon
- autosomal dominant
- dilated microvascular swellings: skin,
hands, fingertips, mucous membrane,
internal organs - nose bleeds, GI bleeds
- can cause iron deficiencies
- swellings bleed when traumatised (little
capillaries near the skin are very sensitive) - total platelet count normal
- coagulation screen will be normal
Management of Hereditary Haemorrhagic Telangiectasia (5):
- iron replacement
- tranexanic acid (anti-fibrolytic prevents
bleeds occurs) - hormonal therapy eg norethisterone
- laser therapy on specific areas
- local measures: nasal packs
Collagen/Connective Tissue Disorders: ehler’s-danlos syndrome:
- is
- clinical signs and blood tests
- management
- fragility of:
- skin
- ligaments
- blood vessels*
- perivascular connective tissue* - easy bleeding and bruising because
collagen is in vessel walls - total platelet count normal
- coagulation screen will be normal
- no specific management but useful to
know if in labour etc
Scurvy:
- is
- clinical signs (3)
- history
- management
- acquired vitamin C deficiency
- bleeding gums
- peri-follicular haemorrhages
- bruises
- must ask: alcohol abuse and diet
- give vitamin C
Thrombocytopenia:
- is
- numbers
- symptoms seen when
- symptoms are
- low platelet count
- normal range = 150-400 x10^9/L
- low = <105 x10^9/L
- symptoms <10 (ish)
- epistaxis, GI bleeds, menorrhagia, bruising,
petechiae/purpura
Disorders of platelet numbers can be
inherited which are rare
acquired which are common
Disorders of platelet numbers: Acquired:
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ITP:
- immune thrombocytopenic purpura
- auto-antibodies against platelets
- leads to platelet removal by spleen
ITP in children:
- acute condition in children
- often follows an infection
- self-limiting
ITP in adults:
- acute/chronic condition in adults
- many potential triggers
- history is key
Are males or females affected more by ITP?
Both are equally affected
Treatment of ITP:
- treat if bleeding or platelets <30 with:
- steroids
- IV immunoglobulins
- TPO agonists (thrombopeotin hormone in
bone marrow causes proliferation) - monoclonal antibodies
- occasionally, splenectomy
Disorders of platelet function:
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-
- clinical features (4)
- x linked recessive mutation
- Haemophilia A: Factors VIII deficiency
- Haemophilia B: Factor IX deficiency aka
christmas disease - Clinical Features:
- spontaneous bleeding into joints and
muscle - chronic debilitating joint disease
- unexpected post-operative bleeding
- family history in most cases (1 in 3 due to
spontaneous mutations)
Coagulation Cascade
insert diagram
- extrinsic: trauma damages blood vessels and exposes cells under the endothelial layer, exposing tissue factor embedded in membrane
F7 in blood binds to TF using calcium making a Via-TF complex
- intrinsic: Circulating factor XII contacts negatively charged phosphates on platelets/subendothelial collagen, activating it to XIIa
Which cleaves XI to Xia
IX to IX a (with Ca)
Meanwhile FVIII starts being cleaved to VIIIa by thrombin
FXIa and VIIIa enter common pathway
Fxa is generated which turns prothrombin (II) into thrombin Iia
Thrombin works as a co enzyme to turn the stabilising factor XIII into XIIIa as well as helping F1 turn into its activated form- 1a aka fibrin
all this thrombin generation ultimately therefore helps form a stable fibrin clot around the platelet plug already formed in haemostasis
X linked recessive inheritance
haemophilia
Carrier mums: have 50% haemophiliac sons
and 50% carrier daughters
All the daughters of affected men become carriers
very rare for a daughter to be affected only if X0
Coagulation disorders on cascade page
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Tests of coagulation
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Blood results in haemophilia A+B
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- intrinsic affected
- extrinsic not affected
- low factor 8 levels in haemophilia A
- low factor 9 levels in haemophilia B
Treatment of Haemophilia
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prophylactic (preventive treatment)
Von Willebrand’s Factor:
- Von willebrand’s factor = large multimeric
glycoprotein - synthesised by endothelial cells and
megakaryocytes - acts as a brdiging molecule between
platelet and collagen at sites of vascular
injury - promotes platelet aggregation
Von Willebrand’s Disease:
- is
- what % of population
- dominant or recessive
- in health does
- in disease causes
- deficiency of Von Willebrand’s Factor and
factor VIII in plasma - most common inherited clotting
abnormality (1% population) - autosomal dominant
- the VW factor carries factor VIII in the blod
and binds platelets to sub-endothelial
collagen - deficiency leads to:
- mucocutaneous bleeds, nose bleeds,
menorrhagia
- clot formation does not happen as it
should in an injury
Blood Results in Von willebrands Disease:
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Treatment of vWD
- desmopressin = increases
synthesis/release - anti-fibrinolytics = tranexamic acid, reduces
thrombus breakdown - plasma products: replace VWF and Facto
VIII
Acquired Haemophilia:
- is
- hence
- how common
- causes
- how to treat
- auto-antibodies act as inhibitors to clotting
factors - effectively renders factor deficient
- rare: acquired haemophilia A most
common - look for underlying driver that has led to
antibody formation:
- malignancy
- autoimmune
- viral
- pregnancy - complex to treat:
- bypassing agents
- immunosuppression
Liver Disease
- defects in synthesis of clotting proteins
- some degree of “auto-anticoagulation”
- bleeding disorders and thrombotic
disorders possible - impaired platelet number and function
What are phagocytes that destroy pathogens like bacteria that enter the liver called?
Kupffer cells e
Vitamin K deficiency
Dietary:
- fat malabsorption
- biliary obstruction (jaundice)
- newborn state
Warfarin:
- PT time (INR) measures extrinsic
pathway
- Factors II,VII,X
Vitamin K dependent Factors:
- X,IX, VII,II and proteins S and C
- required for gamma carboxylation of VK
dependent coag factors turning them from
non-functional to functional forms - Mnemonic: 1972 was the diSCo era
Disseminated Intravascular Coagulation:
- septicaemia: Mengingococcal, endotoxin in
G-ve sepsis - acute promyelocytic leukaemia
- cancer, trauma
- pregnancy complication
- release of tissue factor
- breakdown balance of: coagulation,
fibronolysis - clotting factors and platlets used up
Blood Results in Disseminated Intravascular Coagulation
- prolonged PT, APTT
- low fibrinogen
- low platelets
- raised D-dimer
- raised fibrin degradation products (FDPs)
- red cell fragments on blood film
Treatment of Disseminated Intravascular Coagulation:
- ***treat underlying cause: eg antibiotics
for sepsis - supportive Rx with blood products to try and correct coagulation abnormalities if bleeding
- vitamin K
- consider anti-coagulation
What type of inheritance is seen with Hereditary Haemorrhagic Telangiectasia
1 = Autosomal Dominant
2 = Autosomal Recessive
3 = X-Linked Dominant
4 = X-Linked Recessive
5 = Y-Linked Recessive
1
Bernard Soulier disease is due to a mutation in which molecule?
1 = GP0 2 = GP1b 3 = GP2b3a 4 = GP10a11b 5 = GP123
2
In the absence of bleeding, when might you treat ITP?
1 = When platelets <10
2 = When platelets <20
3 = When platelets <30
4 = When platelets <50
5 = When platelets <150
3
Haemophilia A is the deficiency of which factor
1 = Factor VII
2 = Factor VIII
3 = Factor IX
4 = Factor X
5 = Factor XI
2
In addition to protein S and C, the Vitamin K dependent clotting factors are:
1 = Factors 1,3,5,7
2 = Factors 2,7,9,11
3 = Factors 2,3,5,10
4 = Factors 2,7,9,10
5 = Factors 7,9,11,12
2
The APTT can be used as a screening test for the activity of which pathway?
1 = Common pathway
2 = Extrinsic pathway
3 = Intrinsic pathway
4 = Fibrin pathway
5 = Plasmin pathway
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