Platelets in Pregnancy

what is a clot

an aggregate of activated platelets that has undergone fibrin crosslinking

clotting cascade

a series of enzyme interactions that results in the conversion of prothrombin to thrombin

coagulation

the process of clot formation and homeostasis

coagulopathy

disordered coagulation leading to the inability to form or sustain a clot

factor X (10)

the clotting factor that represents the interaction of the intrinsic and extrinsic pathways, serves to convert prothrombin to thrombin

fibrinogen

an enzyme that, when activated to fibrin, binds platelets to one another, forming a stable clot

fibrinolysis

the process of clot dissolution and breakdown

platelet

a cell fragment derived from bone marrow that forms clots and stops bleeding

prothrombin

an enzyme that, when activated to thrombin, works to cleave fibrinogen to fibrin, enhancing platelet aggregation

throbosis

formation of a clot in a vein or artery

clot homeostasis is what

the balance between hemorrhage and coagulation

what percent of the blood is red blood cells

45%

which is the most dense component of blood

the RBCs

what percent of the blood is plasma

55%

which is the least dense component of blood

plasma

what percent of blood is the buffy coat

<1%

what is the buffy coat of blood composed of

leucocytes and platelets

platelets are produced in the bone marrow by what

megakaryocytes

what is the circulating life span of platelets

10 days

does thrombosis use a positive or negative feedback loop

positive

what are some factors inhibiting thrombosis

active blood flow, endothelial production of prostacyclin, nitric oxide, ADPase

how do inhibiting factors of thrombosis actually suppress platelet activation

preventing inappropriate platelet activation

how is the intrinsic pathway to coagulation activated

as direct result of blood vessel damage

how is extrinsic pathway to coagulation activated

hypoxia, organ damage, sepsis, malignancy, inflammation

how can the extrinsic pathway to coagulation be activated inadvertently in pregnancy

inflammatory conditions such as pre-eclampsia may activate this pathway and cause activation of a clot

both intrinsic and extrinsic pathways flow down to a common pathway. what is the common pathway initiated by

factor Xa (10a)

what are changes that causes hypercoagulability and hyorfibrinolysis in NORMAL pregnancy

significant expansion in plasma volume, changes in the maternal homeostatic system

potentiation of the coagulation system in NORMAL PREGNANCY, confers an increased risk of what…

VTE, disseminated intravascular coagulation (DIC)

what is the leading cause of morbidity and mortality in pregnancy and the post partum period

VTE and disseminated intravascular coagulation (DIC)

what is VWF

Von Willebrand Factor

what is VWF synthesized by

endothelial cells - megakaryocytes

what is the role of VWF

it mediates the adhesion of platelets to sites of injury, promotes platelet-platelet aggression

which factor does VWF carry

VIII (FVIII)

why is VWF upregulated in NORMAL pregnancy (by at least 2x by the time of birth)

to prevent PPH

what is the role of tissue factor

it initiates extrinsic coagulation pathway

where is tissue factor located

at extravascular sites

is tissue factor normally exposed to blood

no

what is tissue factor also essential for APART FROM from initiating extrinsic coagulation pathway

implantation, embryogenesis, angiogenesis

what is tissue factor produced by in pregnancy

placenta and decidua

in which part of the decidua is there found to be a lot of tissue factor

syncytiotrophoblasts

why is tissue factor pathway inhibitor expressed in the human umbilical vein endothelial cells

because you DO NOT WANT A CLOT IN THE CORD geezus

fibrinogen change during pregnancy

increased

VII change during pregnancy

increased

VIII change during pregnancy

increased

X change during pregnancy

increased

XII change during pregnancy

increased

vWF change during pregnancy

incraesed

protein S change during pregnancy

decreased

protein C change during pregnancy

no change

what is the role of protein C

controls facor VIIIa

what is the role of protein S

inhibits factor IXa

pregnancy-induced changes that increase the risk of thrombosis

increased venous distention, decreased drainage (venous outflow), mechanical obstruction by the uterus, decreased mobility, vascular injury

what are some bleeding challenges during pregnancy

placenta detachment leaves large surface with open blood vessels on inside of the uterus. genital damage during birth

although women become hypercoagulable during pregnancy to protect them from bleeding what does it out them more at risk of

developing a blood clot

by how much does pregnancy increase the risk of thrombosis (clot formation)

4-5 fold

what percent of clots are venous

75-80%

what percent of clots are arterial

20-25%

what is the absolute risk of venous thromboembolism in pregnancy

5-20 per 10 000 women

what is the absolute risk of arterial thromboembolism in pregnancy

4 per 10 000 women

what are the risk factors for thrombosis

genetic, acquired

risk factors for venous thromboembolism in pregnancy

acquired/inherited thrombophilia, advanced maternal age, African American, obesity, heart disease, lupus, sickle cell disease, inflammatory bowel disease, smoking, immobilisation

why could an increase in D Dimer in plasma be an indication of severity of coagulopathy

fibrin degeneration releases D Dimer

what is gestational thrombocytopenia

reduced number of platelets (thrombocytes) in pregnancy, where there is a physiological decrease in the maternal platelet count by about 10%

what is the result in thrombocytopenia

increased bleeding, bruising or abdominal blood clotting

what is idiopathic thrombocytopenic purpura (ITP)

an autoimmune condition where a woman’s immune system attacks and destroys her own platelets

how are women with who have been diagnosed with ITP before pregnancy managed until the third trimester

similarly to before pregnancy - typically with glucocorticoids (steroids) as necessary

why is it important to distinguish gestational ITP from autoimmune ITP

because autoimmune ITP is associated with fetal thrombocytopenia

when a woman has ITP what is the percentage of risk for fetal thrombocytopenia

5-10%

what can fetal TP lead to

abnormal bleeding in the newborn, sometimes even prior to birth

when a woman has suspected ITP and not just gestational ITP why will some doctors not perform operative vaginal delivery - forceps or vacuum

due to the possible risk of fetal TP, and bleeding

do women with ITP require c/s

nope

why is it important that a neonatologist is aware of suspected ITP if the newborn is scheduled for circumcision

because they may be at risk of platelet count decrease sharply after birth and may bleed out

how many women develop TP in pregnancy

1 in 10

what percent of TP is gestational in pregnancy

75%

what percent of TP is caused by preeclampsia in pregnancy

20%

what percent of TP is immune in pregnancy

3%

what are treatment options of TP in pregnancy

optimise antenatal iron and hemoglobin, corticosteroids

what is antiphospholipid syndrome

there us reduced antibodies to phospholipids and this reduces coagulation

what is the diagnosis of antiphospholipid syndrome

maternal antiphospholipid antibodies

what are possible obstetric complications of antiphospholipid syndrome

VTE, recurrent miscarriage, FGR, severe pre-eclampsia, intrauterine fetal death

what are some symptoms of thrombosis

asymmetric swelling of lower extremities, usually lower leg, vague back pain, dyspnea, chest pain, cough, increased perspiration

why can thrombosis be hard to find in pregnancy

because many of the symptoms of thrombosis are just common thing is pregnancy

what is a general laboratory testing for thrombosis looking for

D-dimer

how is DVT diagnosed in pregnancy

ultrasound of lower extremities

how is PE diagnosed

chest x-ray

why is it ok to have a chest x-ray for PE in pregnancy

because the risk of PE if remaining undiagnosed is far greater to mum and fetus than radiation exposure

low oxygen saturation even in the setting of a normal chest x-ray should increase suspicion of a PE btw

true

what percent of women with suspected PE will actually have it diagnosed

<10%

what percent of women with suspected PE will be treated after its discovery

<6%

why do we perform diagnostic imaging for PE in pregnancy even with its radiation risk

because if undiagnosed its very serious - death, and clinical diagnosis of VTE is unreliable