clotting disorders Flashcards
what is the clotting cascade
check ipad for full thing but:
intrinsic (damaged tissue): 12-12a, 11-11a, 9-9a, 10-10a
extrinsic (trauma): 7-7a, then with TF to 10-10a
10a activates prothrombin-thrombin, fibrinogen - fibrin
what factors does thrombin activate
5,7,8,11,13
what do protein c and protein s do
prevent constant clotting; protein c and thrombomudulin in presence of protein s stop 10-10a and 13-13a
how does warfarin work
acts on vit-k dependent factors like factors 2, 7, 9,10 and proteins C and S to prevent clotting
what does plasmin do
thrombin converts plasminogen to plasmin, which dissolves the fibrin clot
what is the diagnostic triad for bleeding disorders
personal history of bleeding
family history of bleeding
supportive lab tests
what do you ask about history of bleeding
bruising, surgical and dental history, epistaxis >30 minutes, GI tract bleeding, menses: clots, flooding, duration
urine: haematuria
what do you ask about FH of bleeding
known bleeding disorders; when, where and who tested
surgical history and if abnormal bleeding
what are the main lab tests done for clotting disorders
- FBC
- Hb, haematocrit and WBC
- platelets
- PT = normal 10-12 seconds
- APTT normal is 20-30s
microscopy: large, small platelets or neutrophil or platelet inclusions all indicate certain syndromes
how do you test whether there is a factor deficiency or a coagulation factor inhibitor present?
- do a 50/50 mixture study of patients plasma and normal plasma if times are prolonged
- if inhibitor is present: APTT and PT will still be prolonged
- if deficiency is present: adding in 50% normal WILL correct it; hence could be factor 8 or 9 deficiency
what do you do if nothing is found in the investigations but good bleeding history?
tests for vWD: factor 8, vWF antigen and vWF activity
what are APTT and PT
prothrombin time - measures intrinsic pathway
activated partial thromboplastin time - meausres extrinsic pathway
what does a prolonged PT mean
they are:
- on warfarin
- have a factor 7 deficiency - common
- have a factor 2,5,10 deficiency
what does a prolonged APTT mean
heparin
8,9,11 deficiencies
12 deficiency but no bleeding
vWD (however in types 1 and 2 may be a normal APTT)
what do prolonged both pT and APTT mean
vitamin k deficiency and low fibrinogen = liver disease so malabsorption
disseminated intravascular coagulation (small blood clots form throughout body causing CP, SOB, leg pain etc)
how do you test clot stability and what is it for
euglobin clot lysis (make clot on orange stick, place in fridge, is it still there after 24 hours)
checks for factor 13
what is the physiology of vWF
plasma protein that carries factor 8
endothelilal cells attached to the subendothelial collagen by vWF (they produce it)
stored in welbei-palade bodies
platelets store it as well; helps to clump them together
what is vWD
loss of ability to clot the blood due to defect in vWF or decrease in plasma levels
what are the types of vWD
type 1 - mildest, reduced amount of vwd
type 2 - abnormal vw protein
type 3 - little or no vw protein
how do you test for vwd?
factor 8
vw antigen
vw activity
all normal ranges 50-250
how do you differentiate between type 1 and type 2
ratio of vwF activity: antigen
ratio >0.6 = type 1
ratio <0.6 = type 2
symptoms of type 1 vwd
bruising, menorrhagia, mucosal bleeding
treatment of type 1 vwd
DDAVP (desmopressin) and transexamic acid
increase level of vw protein, for last 24 hours
watch for diminishing returns in major surgery bc may need to give vwF
how does DDAVP work
increases vWF secretion from endothelial cells
what is the issue with type 2 vwd
clinically indistinguishable from type 1
what is type 2b
overactive protein (abnormal) which results in thrombocytopaenia
avoid desmopressin bc increases vwF from endothelial cells and don’t need an increase
to diagnose from type 2: give DDAVP when well and meausre BP and iron ?
how do you treat type 2b
vwF concentrates or replacement therapy
how do you treat type 2
DDAVP
what is type 3 vwd
severe, life threatening
serious mucosal bleeding and operative treatment will cause severe bleeding
what is haemophilia
is a genetic disorder that is inherited and impairs clotting, there are 3 types but 2 main ones (A and B)
what is haemophilia A
reduction in factor 8
what is haemophilia B
reduction in factor 9
what is haemophilia C
known as plasma thromboplastin antecedent (PTA) deficiency = mild form of haemophilia affecting both sexes due to factor 11 deficiency
how do you grade haemophilia in terms of severity?
factor level, <1, 1-5, >5 (severe, moderate, mild)
bleeding: spontaneous, slight injury, trauma
frequency: 1-2x a week, 1x per month, rare
how is haemophilia A treated?
home therapy (explained in another FC) DDAVP useful for mild haemophiliacs, it raises levels by 2 or 3; given SC, IV or intranasally
also transamexic acid
haemophilia B differences
factor 9 - recombinant small molecule; bigger distribution than above
amount needed = rise x weight
how does transamexic acid work
anti-fibrinolytic agent, given orally, which slows down the plasminogen system allowing any clot that’s formed to stay longer
what is the home therapy for haemophilia?
primary - start when patient is 18 months - 3 years old
secondary - start after 3 joint bleeds
injections:
factor 8 - alternate days but still often 3x a week
factor 9 - 2x a week
what is a VTE
DVT and PE
physiology of blood in legs
contraction of calf muscles normally squeeze blood up the deep veins of the leg and internal venous valves prevent it flooding back
in diseased states: varicose veins bc systems don’t work well so back wash of blood, veins bulge and blood pools in the deep veins
what is virchow’s triad
stasis of blood flow (immobile)
endothelial injury - esp leg operation
hypercoagulability - acute phase reactant proteins including fibrinogen, factor 8 and vWF
what are the risk factors for VTE
-hip or knee replacement surgery patients
-anasthesia
-post-op period bed rest
> 60 years
-prev DVT or family history of DVT
how do you prevent DVT
mechanically: pneumatic compression stockings
pharmacologically: low does LMWH or low dose unfractionated heparin
direct anti-Xa and DOAC’s
how do you manage a suspected VTE
do not investigate first unless this can be done within 1 hour for PE or 4 hours for DVT
- use LMWH or UFH heparin, or clexane
- at the same time, begin oral warfarin for 48-72 hours until INR is 2 then discontinued
how is warfarin reversed
vitamin K1, and immediately via prothrombin complex concentrate and FFP
what is the pathophysiology of the thrombus
-dissolution
-propagation
-recanalization - growth of SMC, fibroblasts and endothelium to form a fibrin rich thrombus –> capillaries may form into the thrombus, providing further nutrient supply to the clot
embolisation
what is an embolus
-material which is transported in blood stream and lodges in a blood vessel at a different site
when it impedes or blocks blood flow in artery = embolism
what causes a DVT
clot, muscle haematoma, baker’s cyst or cellulitis
what are the 4 most common signs of a DVT
warm, swollen, tender on palpation and in calf, redness
also: homan’s sign: pain in calf upon dorsiflexion of ankle
pathophys of a PE
thrombus breaks off, travels in venous system into right atrium, to pulmonary arteries and blocks it
what is a massive PE
large clot which lodges in right side of heart or in both pulmonary arteries
classically presents with syncope and other symptoms of PE
clinically defined as a massive PE by presence
physical signs of a PE
-increased respiratory rate
-tachyarrhythmias
-possible signs of DVT
-pleural rub can be heard
-sudden onset of pleuritic chest pain and worse on breathing in
(sharp pain)
- shortness of breath
- haemoptysis
how do you compare leg swelling and checking for DVT
-measure 10 cm down from tibial tuberosity
what are the investigations for a PE
ECG; right heart strain like RBBB
CHEST x ray
ABG: hypoxia, type 1 resp
how do you diagnose a PE
look at diagram in notes - wells score
what are the investigations for a DVT
0 on wells score = lower risk
no need for doppler but d-dimer anyway
if d-dimer is positive, then do a doppler and a CTPA
if higher clinical probability = go straight for doppler on CTPA
how do you manage a PE
LMWH followed by doac’s; however if religious reasons give fondaparinux bc porcine in heparin
what are the guidelines for doac’s
apixaban or rivaroxaban
to TREAT DVT or PE:
- 15mg rivaroxaban should be taken twice a day for 21 days and then 20mg oD for 3 months
if these are not suitable; LMWH for at least 5 days followed by dabigatran or edoxaban or LMWH concurrently with a VKA (warfarin) till therapeutic anticoagulation
what is the well’s score
for DVT >2
for PE>4
