Download Laboratory investigation of easy bruising and menorrhagia

Investigation of easy
bruising and heavy
menstrual bleeding
Almero Du Pisani
NHLS Groote Schuur Hospital
COAGULATION OVERVIEW
TESTS & LIMITATIONS
Haemostasis
• Blood vessels
• Platelets and Von Willebrand’s Factor
• Coagulation factors
HAEMOSTASIS: The big picture
The “Cascade Model” of coagulation
aPTT
PT/INR
TT / Fibrinogen
Coagulation test limitations
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Not natural
Biological variation
Confirmatory not for screening
Insensitivity to clinically important bleeding
disorders:
– Mild Haemophilia A, mild VWD
– Not testing FXIII
• Prone to artifact
Problems with PTT
– Various activators used
– FVIII, IX and XI deficiency but also:
• Inhibitors (therapeutic and aPL AB)
• FXII (clinically insignificant)
– Variability of reagents – different sensitivity to deficiency, aPL
AB, inhibitors and heparin
– Lack sensitivity to milder deficiency especially fibrinogen and
prothrombin
– Physiological states – pregnancy – increased FVIII – may
miss mild Haemophilia A and VWD
Problems with PT (INR)
• FII, VII, IX, X deficiencies picked up (also acquired
DIC, Vit. K and liver)
• INR designed for warfarin monitoring
• Differences in activator (TF)
• Also low sensitivity at intermediate decreased
levels
• Very occasionally affected by aPL AB
Problems with bleeding time
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Poorly reproducible
Technique related
Poor sensitivity and specificity
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Influenced by:
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Meds: NSAID
Renal failure
Severe anaemia
Thrombocytopenia
Paraproteins
 Prolong BT – no correlation with clinical bleeding
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BT may be normal in VWD, Platelets storage pool disorders
 Not recommended
PFA-100, TEG and TGA
Lets chat about PFA-100 later!
But TEG have still not made it into routine
testing
TGA promising, but also still a long way off
before it can be used
Problems with basic vWB screen
(antigen and RiCo)
• Extremely error prone:
– Pre-analytical specimen handling
• Influence by inflammation, stress,
pregnancy, blood group, menstrual cycle
and oral contraceptives
• ??Lowest at 1-4d cycle
• Repeat testing
So apparently the patient bruises easily
- who should I test?
What is recommended?
If suspected bleeding disorder (from structured bleeding
questionnaire) before surgery or work up of easy
bruising:
www.isth.org/resource/resmgr/ssc/isthssc_bleeding_assessment.pdf
– aPTT / PT and FBC
– Discourage BT
– PFA-100 is useful (American Family Physicians)
• Superior to bleeding time
• Sensitivity: VWD and other platelet disorders 90% with 86 –
94% specificity
• Negative PFA – not exclude VWD / other platelet disorders 
revise history  other testing
PFA-100
• Two cartridges:
– ADP/Collagen
– Adrenalin/Collagen
• Closure of aperture by platelet clot
• However - British Anaesthesia June 2009
– Sensitivity:
• 70% VWD (using both cartridges)
• 58% other platelet disorders
– But better than BT (29% VWB, 33% platelet disorders)
So what to do?
Bleeding questionnaire indicative of significant
risk, family and drug history taken into account:
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FBC & platelets with smear morphology
PT / PTT / Fibrinogen
Iron studies is suspecting anaemia
vWB screen
Possibly PFA-100
Strong enough history – platelet aggregation
studies
What about heavy menstrual
bleeding?
Menstruation
• “Heaviness” depends on:
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Hormone levels
Vasoconstriction
Muscular contraction in the uterus
Haemostatic function
• “Normal menstruation”
– frequency between day 24 and 38
– 4.5 and 8 days long
– 5 - 80 ml per cycle
Heavy menstrual bleeding
• 10–35% of women in their lifetime
• 5% of women consult a physician
• NICE: HMB = “excessive menstrual blood
loss which interferes with a woman’s
physical, social, emotional and/or material
quality of life”
History
• HMB or not – coloured by cultural experience
• Difficult to quantify – techniques used in clinical trails
not practical
• Questionnaires – none perfect
• Have to individualise and look at – length, duration,
volume, flow/clots, variability & how it impacts on her
life
Classification of HMB
Structural
• Polyp
• Adenomyosis
• Leiomyoma
• Malignancy and hyperplasia
Non-structural
• Coagulopathy (20% of non-structural)
• Ovulatory dysfunction
• Endometrial
• Iatrogenic
Other
Can history help to find the cause
of HMB?
• Anovulatory - Symptoms of ovulation absent
• Structural - Bleeding between periods, post-coital
bleeding, dyspareunia, vaginal discharge and pelvic
pain
• Haemostatic defect or adenomyosis – regular,
cyclical but heavy
• Endocrine - headaches, breast discharge, changes in
hair growth/pattern, acne, and hyper- or
hypometabolic changes
Cause of coagulopathy
• vWB disease (84% have HMB)
• Haemophilia carriers
• Platelet dysfunction
• Vessel wall abnormalities eg. Hereditary
haemorrhagic telangiectasia, Ehlers Danlos
Finding the cause of the
haemostatic defect
• Family or personal history of other bleeding
(spontaneous or provoked)
• Did it need treatment?
• Other medical conditions – endocrine (thyroid),
liver, kidney, bone marrow pathology
• Drugs – antiplatelet, anticoagulants, hormones,
natural / diet
Physical examination – focus to
find underlying bleeding disorder
• Primary haemostatic failure – petechiae,
purpura, ecchymoses, gum bleeding
• Secondary – muscle and join bleeds
• Vascular - dermal / subdermal
telangiectasias
Which examinations and investigations should
be performed (finding coagulopathy as cause)?
– FBC and smear (patelet morphology, anaemia
(microcytic)
– PTT / PT (INR) / TT / Fibrinogen
– VWB screen – Day 1-4 of menstruation –
repeat
– Platelet function testing (aggregometry and
release assays)
– Iron studies
References