Protein C S Deficiency

Question 1

what causes acquired protein C and S deficiencies?

Answer 1

• liver disease
• vitamin K deficiency
• chemo

Question 2

what causes inherited forms of protein C and S deficiencies?

Answer 2

a genetic mutation in the gene for either protein C or S causes either a quantitative problem (a decreased amount of protein C or S) or a qualitative problem (protein C or S that doesn’t work well)

Question 3

what does protein S do?

Answer 3

protein S acts as a cofactor to enable the function of protein C

this means that without protein S, protein C cannot do its job

Question 4

what does protein C do?

Answer 4

when active, it inactivates factor Va and VIIIa

it’s an anticoagulant because it stops the coagulation cascade!

without the anticoagulant effects of proteins C and S, the blood is more prone to clotting

Question 5

what happens when there’s protein C or S deficiency?

Answer 5

blood clots

because you don’t have protein C and S to keep the coagulation cascade in check

thrombophilia

Question 6

what medical conditions can result from hereditary protein c or S deficiency?

Answer 6

• DVT
• PE (less common)
• ischemic strokes
• budd-chiari syndrome

DVTs in patients with protein C and protein S deficiency are often unprovoked or recurrent

Question 7

what are provoked DVTs?

Answer 7

DVTs that occur in the presence of known thrombosis risk factors, such as immobility, cancer, or recent surgery

Question 8

what are unprovoked DVTs?

Answer 8

DVTs that occur in the absence of any discernible risk factors.

Question 9

What is the most common presentation of protein C and protein S deficiency?

Answer 9

DVT

Question 10

what is warfarin?

Answer 10

anticoagulant

Question 11

what’s the most dangerous side effect of warfarin?

Answer 11

warfarin- induced skin necrosis

a potentially lethal condition that causes skin and subcutaneous tissue thrombosis and necrosis

Question 12

why are patients with protein C and S deficiencies at a high risk for warfarin-induced skin necrosis?

Answer 12

warfarin blocks the production of vitamin K-dependent coagulation factors, which includes proteins C and S

these factors require carboxylation of glutamate residues in order to be functional

vitamin K needs to be in its reduced form for that carboxylation to happen

once vitamin K participates in the carboxylation process it becomes oxidized, but it soon returns to its reduced state with the help of the enzyme vitamin K epoxide reductase

warfarin inhibits epoxide reductase so vitamin K is stuck in its oxidized form and it can’t participate in the carboxylation of glutamate so all the vitamin K dependent cofactors like protein S and C aren’t synthesized

go look at the diagram…

Question 13

which coagulation factors are vitamin K dependent?

Answer 13

factors II, VII, IX, X, and proteins C and S

Question 14

what is a heparin bridge? when is it used?

Answer 14

when you start a patient on warfarin for the first time - particularly in patients who have known protein C or S deficiency!

when you give warfarin, proteins C and s are the first proteins to decrease = hypercoagulation state

usually, this transient hyper coagulable time doesn’t cause clinical effects but if the patient already has a protein C or s deficiency and is already clotting a lot then the results can be catastrophic!!

so you give heparin to prevent this

Question 15

Why is there a period of hypercoagulability in initiating treatment with warfarin?

Answer 15

warfarin inhibits vitamin K dependent enzymes like protein C & S

protein C& S become dificient right after you give warfarin = hypercoagulation

it takes a couple days before the other vitamin K dependent factors are effected by warfarin

protein C and protein S become deficient before factors II, VII, IX, and X are deficient

Question 16

what is pupura fulminans?

Answer 16

patients with protein C or protein S deficiency are at risk to get this!

an acute disorder in characterized by nonstop thrombotic complications

Question 17

how does pupura fulminans present clinically?

Answer 17

present suddenly, usually with hemorrhagic necrosis and infarction of the skin, due to widespread, multiple thrombi

initial clinical presentation may mimic immune thrombocytopenic purpura or thrombotic thrombocytopenic purpura

BUT PF progresses to necrosis much more rapidly than these other diseases

Question 18

in what clinical conditions is purpura fulminans common?

Answer 18

• protein C or S deficiency
• severe sepsis
• disorders that reduce protein synthesis capacity, such as severe liver disease

Question 19

when do patients who are homozygous vs. heterozygous for protein C or S deficiency first present with symptoms?

Answer 19

homozygous = present at birth

heterozygous = typically have an inciting factor, such as infection

Question 20

How is purpura fulminans distinguished from disorders such as immune thrombocytopenia purpura?

Answer 20

rapid development of necrosis and bullae

Question 21

is protein C or S deficiency more common?

Answer 21

protein C deficiency is more common

protein C deficiency is the most common thrombophilia after Factor V Leiden and prothrombin G20210A mutation

Question 22

A patient presents with his second unprovoked deep vein thrombosis. What is the most likely disorder responsible for this?

Answer 22

Factor V Leiden

Question 23

how do you diagnose protein C and S deficiencies iency?

Answer 23

direct protein assay of protein blood levels

strong clinical suspicion like individuals with recurrent, unprovoked, or unusual thrombosis at a young age you should get a workup

lab studies that show low protein C or S levels (<50% of normal)

Question 24

A 3-day-old male is admitted to the hospital with widespread purpura and a low platelet count. His family history is significant for a father who had recurrent deep vein thromboses, and a mother who suffered a severe skin condition after taking an anticoagulant medication. What is the most likely diagnosis?

Answer 24

purpura fulminans

Two hits to one protein lead to a severe deficiency that can result in spontaneous formation of purpura fulminans

One hit to the protein often requires a trigger, such as infection, to cause purpura fulminans

resulting hypercoagulability enables widespread clots that progress from skin pain and erythema to skin necrosis and finally to disseminated intravascular coagulation