hemostasis

Question 1

what is the algorithm of homeostasis ?

Answer 1

vascular spasm occurs when a vessel wall is severed or punctured - the endothelin released by endothelial cells and pain receptors causes contraction of smooth muscle cells

platelet plug formation starts -
platelets are activated by chemicals released from the injury site and by contact with subendothelilal collagen
von Hillebrand factor helps stabilise the platelet plug
the platelets themselves now release chemicals to attract other platelets

then there is coagulation - fibrinogen is converted to fibrin
a mesh forms that traps more platelets and erythrocytes

Question 2

what is the morphological characteristics of a blood clot ?

Answer 2

gelatinus but robust clot made up of a mesh of fibrin

Question 3

what are the pathways for homeostasis ?

Answer 3

the extrinsic pathway - triggered by damage occurring to surrounding tissues

the intrinsic pathway - begins in blood stream and triggered by internal damage of the vessel wall

both of these merge into a third pathway - called the common pathway

Question 4

all the three pathways in homeostasis are dependant on what ?

Answer 4

calcium and vitamin K

Question 5

clotting factors are derived from where

Answer 5

liver and platelets

liver needs vit K to produce many of them

Question 6

the intrinsic or the extrinsic pathway is more quicker responding ?

Answer 6

the extrinsic pathway - tissue factor pathway

Question 7

what is the cascade of the extrinsic pathway?

Answer 7

damaged extravascular cells come in contact with the blood plasma

they release factor 3 (thromboplastin/ tissue factor)

then factor 7 is activated by factor 3 to factor 7a

then a tissue factor and 7 a enzyme complex is made

leading to activation of factor 10 with calcium to 10a

leading to the common pathway

Question 8

what is the process of activation in intrinsic pathway ?

Answer 8

when factor 12 come in contact with foriegn materials , negatively charged molecules
it becomes activated
or there can be surface activation

factor 12a —-> factor 11a —–> factor 9a ——> factor 10a

Question 9

what is the common pathway

Answer 9

factor 10a —-pro thrombin —-> thrombin

thrombin—– fibrinogen —- soluble fibrin —–> polymerised fibrin clot

Question 10

what is fibrinolysis ?

Answer 10

protien plasminogen converted to active plasmin breaking down the fibrin of the clot

bradykinin is a vasodilator
reversing effects of serotonin and prostaglandin’s from platelets - smooth muscles in the walls relax

Question 11

what are the anticoagulants?

Answer 11

protein C

tissue factor pathway inhibitor - inhibits factor 7 activation

antithrombin inactivates factor 10
opposes conversion of prothrombin

basophls releasing heparin - also opposing porthrombin

heparin found on the surfaces of cells lining the blood vessels

Question 12

what are the types of homeostasis ?

Answer 12

primary hemostasis

secondary hemostasis

Question 13

what are the characteristics of primary hemostasis?

Answer 13

refers to platelet reactivity at the site of vessel injury

the onset is spontaneous immediately after trauma

sites - skin and mucus membranes

form - petechiae , ecchymosis, purpura

other sites - rare

clinical examples - thrombocytopnea , platelet defect - in number and function , von willebrand disease , scurvy

Question 14

what is the characteristics of secondary homeostasis ?

Answer 14

coagulation of plasma due to coagulation factors - intrinsic system , extrinsic system and common pathway

delayed after trauma

sites - deep tissues

forms - hematomas

other sites - joint , muscle , CNS , retropeitoneal space

clinical examples - factor deficiency , liver disease , acquired inhibitors

factor deficiency
hemophilia A - factor 8 deficiency

hemophilia B - factor 9 deficiency

Question 15

what is APTT induced by ?

activated partial thromboplastin time

Answer 15

asses the intrinsic system and common pathway

surface contact activation
factor 12 in the presence of artificial negatively charged particles (phospholipid) is activated
and calcium

addded to sodium citrate- rversable chelator of calcium

Question 16

what is PT induced by ?

Answer 16

asses the extrinsic pathway and common pathway

excess of tissue factor / thromboplastin (reconbiant human or isolated animal tissue factor) , with exogenous phospholipid

and calcium
allowing factor 7 to overcome the inhibitory effects of TFPI and favouring activation

Question 17

what is thrombin time?

Answer 17

time for fibrinogen to go to fibrin

direct measure of fibrinogen function

adding purified exogenous thrombin

Question 18

in APTT examination what should be the ratio of anticoagulant to blood plasma ?

Answer 18

1 :9

anticoagulant / sodium citrate : blood plasma

Question 19

which assay serves as the basis for internationally normalised ratio (INR)?

Answer 19

PT - prothrombin time

for oral anticoagulant monitoring such as warfarin measurement

Question 20

what is INR ?

Answer 20

ratio of patient prothrombin time / mean of normal prothrombin time in local lab - on normal individuals

rasied to the power of international sensitivity index

Question 21

in patients with non warfarin treatment what is used to measure the homeostasis ?

Answer 21

pt vales in seconds

Question 22

antigen assays establish what ?

Answer 22

presence of coagulation factors

Question 23

combining antigen assays and coagulation based assays which measure the function does what ?

Answer 23

characterize any protein with reduced function but with normal antigen levels - dysfunctional proteins or inhibitors

A dysfunctional protein has reduced protein function with normal levels of antigen.

The most useful means to determine whether fibrinogen is abnormal (i.e., dysfibrinogenemia) is to measure clottable fibrinogen and fibrinogen antigen
If fibrinogen clottability is less than 90% of the amount of fibrinogen antigen present, this finding would suggest that the protein produced is abnormal in some way

Question 24

what are chromogenic assays used for ?

Answer 24

used to measure certain enzymes (plasmin, activated protein C) and various plasma protease inhibitors (antithrombin, C1 inhibitor, α2-antiplasmin, PAI, tPA).

measure the therapeutic levels of unfractionated heparin, low molecular weight heparin, or fondaparinux

Question 25

what are the findings and diagnosis associated with it ?

Answer 25

if aPTT is long and PT and TT normal ``` intrinsic factor defects factor 8 deficiency haemophilia A factor 9 deff - hemophilia B ONLY IN MALES factor 12 deficny ``` contact deficiency - no bleeding factor 11, prekalikrien, high molecular weight kininogen lupus anticoagulant PT long , and aPTT and TT normal ? extrisic factor defect factor 7 deficiency (deficiency of fibrinogen , factor 2 , factor 5 , factor 10) TT long , aPTT and PT normal? fibrinogen defect - fibrinogen deficiency - by 30-40 percent detectable low conc of fibrinogen inhibitors aPTT and PT long , TCT normal common pathway - thrombin- factor 2 , factor 5 , factor 10 defect or deficiency combined deficiency vit K dependant - thrombin (factor 2) factor 7 , factor 9 , factor 10 diffrential diagnosis : anticoagulation therapy , DIC - sepsis , maligancy , obstetrics , abrution of placenta , surgery of uterus / prostate gland liver disease , vit k deficiency massive transfusions all tests long sever deficiency in fibrinogen high conc inhibitors of fibrinogen combined deficiency of fibrinogen , intrinsic and extrinsic pathways

Question 26

hemophilia A and B has hat type of hereditary pattern ?

Answer 26

X linked recessive disorder females can be carrier males are affected or de novo mutation one third of haemophilia A

Question 27

which type of haemophilia can affect women and how?

Answer 27

Hemophilia a can affect women through lyonisation of the normal x chromosome turner syndrome xo daughter of affected male and carrier female

Question 28

severe hemophilia has what clinical presentation ?

Answer 28

spontaneous bleeding two or four times a month | needs replacement of factor therapy

Question 29

mild hemophilia has what clinical presentation ?

Answer 29

prolonged bleeding after trauma or major surgery - rarely need iv factor replacement

Question 30

mild to moderate deficiency of Factor 8 for whom a diagnosis of hemophilia A may be less apparent needs more diagnostic why ?

Answer 30

for a female patient with factor 8 defficiency that is autosomal inheritance von Hillebrand disease - secondary deficiency of factor 8 may occur - because factor 8 is normally bound to von willebrand factor

Question 31

what is haemophilia b leyden ?

Answer 31

factor 9 levels at childhood 75 percent of adulthood increases during post puberty - result of steroid hormone action hemophila B leyden - present with haemophilia b in childhood ranging from 1-33 percent , plasma levels rise to 70 percent after puberty and the bleeding complication resolves

Question 32

what is the standard treatment for haemophilia a and b ?

Answer 32

recombiant factor products inhibitor antibodies to favtor 9 and 9 - complicated therapy

Question 33

Afibrinogenmia is what type of inheritance ? | and what are its clinical manifestations

Answer 33

autosomal recessive - represent tota absence of fibrinogen umbilical stump , mucosal bleeding , musculoskeletal and cns bleeding poor wound healing associated with recurrent miscarriage , and antepartum and postpartum haemorrhage

Question 34

what is hypofibrinogenima clinical manifestations

Answer 34

milder form of bleeding associated with reoccurring misscarriage and antepartum and postpartum haemorrhage

Question 35

what is the cause of dysfibrinogenemia?

Answer 35

associated with liver diseases - post transitional modifications common in hepatitis b and C

Question 36

what is the clinical manifestation of dysfibrinogenemia ?

Answer 36

usually asymptomatic , have mild bleeding some cases thrombosis with or without bleeding history

Question 37

what is the diagnosis of DIC ?

Answer 37

prolonged APTT and PT reduced fibrinogen and platelet count - thrombocytopnea in prothrombtic state -normal PT and APTT mildly reduced platlet count and normal or elevated fibrinogen made through - test showing simultaneous presence of thrombin and plasmin formation D - dimer essay confimatroy test positive - both thrombin and plasmin form