Investigation of easy bruising and heavy menstrual bleeding
Almero Du PisaniNHLS Groote Schuur Hospital
Coagulation test limitations
• 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
• Poorly reproducible• Technique related• Poor sensitivity and specificity
• Influenced by:– Meds: NSAID– Renal failure– Severe anaemia– Thrombocytopenia– Paraproteins
Prolong BT – no correlation with clinical bleeding
• 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
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/isth-ssc_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:
• FBC & platelets with smear morphology • PT / PTT / Fibrinogen• Iron studies is suspecting anaemia• vWB screen• Possibly PFA-100 • Strong enough history – platelet
aggregation studies
Menstruation
• “Heaviness” depends on:– 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