abnormalities of haemostasis

Question 1

what are minor bleeding symptoms

Answer 1

easy bruising

gum bleeding

frequent nosebleeds

bleeding after tooth extraction

post op bleeding

menorrhagia

post partum bleeding

Question 2

what are signs of abnormal bleeding *

Answer 2

epistaxis not stopped by 10mins of compression or requiring medical attention/transfusion

cutaneous haemorrhage or bruising w/o trauma

prolongued bleeding from trivial wounds - .>15mins or in oral cavity, or recurring spontaneously 7 days after wound, or spontaneous GI bleeding leading to anaemia

menorrrhhagia requireing treatment or leeading to anaemia - not due to structural lesions

eavy or recurrent bleeding after dental extractions or surgery

Question 3

what are the 2 branches of abnormal haemostasis *

Answer 3

lack of a specific factor - failure of production (congenital or acquired), increased consumption/clearance

defective function of a specific factor - genetic defect, acquired defect (drugs, synthetic defect, inhibition) - acquired more common

Question 4

summarise platelet adhesion and aggregation

Answer 4

when collagen exposed, platelets bind to VWF or straigt to collagen

platelet release ADP and thromboxane

exposing GIpIIb/IIIa wich bind platelets together

Question 5

causes of thrombocytopenia *

Answer 5

bone marrow failure (failure of production) - leukaemia (proliferation of clone mean squeeze out haemopoeisis), B12 deficiency (ave enourmous immature cells that cant make dna = suppressed haemopoesis)

accelarated clearance - immune thrombocytopenia (destroyed in circ), DIC - shortened half life

hypersplenism - increased pooling of platelets in spleen and shortened half life

Question 6

describe auto0-immune thrombocytopenic pura pura*

Answer 6

have anti-platelet autoantibodies

tey coat platelet

platelets removed by reticulo-endothelial system - ie by macrophages of the spleen

this is common

Question 7

how can impaired function cause primary haemostasis *

Answer 7

hereditary abscence of glycoproteins or storage granules - ie the storage of things needed for coagulation

acquired due to drugs - aspirin, NSAIDS (thrombaxane A2 synthesis is interferred), clopidogrel

Question 8

bleeding pattern with Glanzmann’s thrombocytopenia *

Answer 8

bleed severely

becasue affects platelet aggregation

Question 9

what are the roles of VWF *

Answer 9

bind to collagen and capture platelets

stabalise factor 8

Question 10

describe von-willibrand disease *

Answer 10

hereiditary - common - autosomal

can be acquired dur to Ab - rare

type 1 - make some vwf - doesnt survive long ion the circulation

type 2 - vwf abnormal function

type 3 - dont make any - recessive

platelets dont stick as well - weak platelt plug

Question 11

disorders of the vessel wall that interrupt coagulation *

Answer 11

inherited - rare - hereeditory haemorrhhagic telangiectasia ehler’s danlos syndrome and other connective tissue disorders

acquired - scurvy, steroid therapy (thin connective tissue holding vessels - more likely to bleed), aging (age related purpura - thinning of connective tissue), vasculitis (inflammation of bv)

Question 12

what can be affected in bleeding disorders in primary haemostasis *

Answer 12

vessel wall

platelets

vwf

Question 13

what is the pattern of bleeding for primary bleeding disorders *

Answer 13

immediate

prolongued bleeding from cuts

epistaxis

gum bleeding

menorrhagia

easy bruising

superficial bleeding into skin and mucous membrane

prolongued bleeding after trauma or surgery

petechiae - ONLY WITH THROMBOCYTOPENIA

if have severe vwd - haemopilia like bleeding becasue factor 8 wopuld also be low

Question 14

how can you test for disorders of primary haemostasis *

Answer 14

platelet count and morphology - need EM

bleeding time - not done anymore unless need to test vessel wall function- not sensitive or specific

now - PFA100 in lab: - recreate sheer stress, collagen and things to stim platelets - assesses platelet dysfunction and vwf activity

assays of vwf - measure and look at aspects of function

clinical observation

Question 15

what is the difference in the generation of thrombin in normal people compared to haemopiliacs, consequence of this on coagulation *

Answer 15

normal have large thrombin burst

deficiency in any clotting factor prevents this burst from happening and so stops te convertion of fibrinogen to fibrin - therefore primary plug falls apart

Question 16

what are the 2 branches of disorders of coagulation *

Answer 16

deficiency of coag factor production

increased consumption of coag factors

Question 17

list disorders of coagulation - deficiency of coag factor production *

Answer 17

hereditory - factor 8/9 - haemopilia A or B

acquired (more common) - liver disease (coag factor syntesis reduced), dilution (when replace red cells in transfusion but not the plasma = reduction of coag factors), anticoag drugs eg warfarin

Question 18

what are the bleeding patterns of different coagulation defiencies *

Answer 18

factor 8 and 9 - haemopilia - x linked - severe but compatable with life - spontaneous joint nad muscle bleeding

protrombin (factor 2) - lethal

factor 11 - can have low levels, bleed after trauma but not spontaneously

factor 12 - no excess bleeding

Question 19

list disorders of coag - increased consumption *

Answer 19

acquired:

disseminated intravascular coagulation

immune - autoAb for clotting factors

Question 20

describe disseminated intravascular consumption *

Answer 20

there is general activation of coagulation because of tissue factor - unregulated turning on of coag system

it is associated wit tissue damage, sepsis, cancer and obstetrics and inflammation

lots of clotting - leads to consumption of all clotting factors and platelets = bleeding because no longer have enough factors

activates fibrinolysis - depletes fibrinogen

deposition of fibrin in vessels and organs causes organ failure

Question 21

describe bleeding in coagulation disorders *

Answer 21

superficial cuts dont bleed - platelet plug still work

bruising common

nose bleeds rare

spontaneous bleeding deep - into muscles and joints - haemarthrosis

bleeding after trauma may be delayed and is prolongued

bleeding frequently restarts after stopping

Question 22

what are the tests for coagulation disorders *

Answer 22

screening tests:clotting screen (protrombin time and activated partial thromboplastin time), full blood counts for platelets

factor assays eg for factor 8

test for inhibitors

Question 23

describe the clotting screen *

Answer 23

APTT looks at intrinsic system - factors 12, 11, 8, 9, 5, 10, 2 - used to monitor levels of heparin given and diagnose haemophilia

PT looks at extrinsic system - factors 7, 5, 10, 2 - used to control levels of anticoag eg warfarin

look for time takes for 1st strands of fibrin to form

so if aptt prolongued - deficiency in 12, 11, 8, 9 - but not in common factors if pt is fine

both tests used to diagnose DIC

Question 24

what are the limitations of routine clotting tests *

Answer 24

some bleeding disorders are not picked up, so need specialist tests

mild factor deficiencies

vwd - unless it as caused low factor 8

factor 8 defiency - cross linking

excessive fibrinolysis

vessel wall disordersmetabolic disorders eg uraemia

thombotic disorders

Question 25

list te disorders of fibrinolysis*

Answer 25

rare

hereditory - antiplasmin deficiency

acquired - tPA drug, DIC (lots of trombin leads to lots of fibrinolysis)

Question 26

describe the genetics of haemolpilia *

Answer 26

x linked recessive

lyonisation (random inactivation of x chromosome means there are varying levels of haemopilia and levels of factor 8)

Question 27

describe the genetics of vwd

Answer 27

autosomal

1 in 2 chance of passsing on to eiter gender

type 1 and 2 - autosomal dominant

type 3 - autosomal recessive

Question 28

what is the genetics of common bleeding disorders, other than haemophilia and vwd

Answer 28

autosomal recessive

Question 29

what is the treatment for failure of production of factors or platelets *

Answer 29

replace them

prophylactic or therapeutic

stop drugs if iatrogenic

Question 30

what is the treatment for bleeding disorders caused by immune destruction *

Answer 30

immunosuppression - prednisolone

splenectomy for itp (rare) - where destruction is happening

Question 31

how would you treat abnormal haemostasis caused by increased consumption eg dic *

Answer 31

treat the cause

replace as necessary

Question 32

describe factor replacement therapy *

Answer 32

plasma contains all of the coagulation factors - spin plasma an dtake off precipitate (cyroprecipitate) which is rich in fibrinogen, factor 8, vwf and factor 13

factor concentrates - available for all factors except factor 5 - all donation go into 1 vat and differnet factors are fractionated off , also have prothrombin complex concentrates containing factors 2 7 9 and 10 - to reverse warfarin

now use recombinant forms of 8 and 9 - have to use concentrates for rare things

Question 33

describe how ddvap is used to treat primary haemostatic problems *

Answer 33

it is desmopressin - synthetic analoigue of ADH which causes endo cells to make vwf

good if deficient in vwf - dont work if vwf production is defective

cause 2-5x increase in endogenous stores

Question 34

describe how transexamic acid increases clotting *

Answer 34

inhibits fibrinolysis by competing with fibrin for tissue plasminogen activator

useful for all clotting disorders

Question 35

list other treatments for clotting disorders *

Answer 35

bispecific antibody mimics factor 8 - doenst cause rejection

use ab that prevents tfpi fo taht tissue factor is not switched off = increase in clotting

antithrombin RNA inhibitor - stop antithrombin production = more clotting

gene therapy

platelets from donation

fibrin glue/spray

Question 36

if daughter of person with haemophilia is pregnant what is the probabilty they have an affected son

Answer 36

they are obligate carrier - had to get x from dad and haemophilia is x linked

50% chance having boy

therefore 25% chance affected boy

Question 37

the daughter of a female carrier of haemophilia is pregnant;

probability of male affected son

scan confirms male - probability affected

genetic testing confirms she is carrier - probabilty that the son is affected (still know male from scan)

Answer 37

12.5% - 50% chance she is carrier, 50% male, 50% he is affected

25%

50%