Investigation of easy bruising and heavy menstrual bleeding

Almero Du PisaniNHLS 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

• 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

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/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

What about heavy menstrual bleeding?

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

References