A term boy is well at birth, but at 30 hours he develops spreading purple-black skin lesions on his legs and buttocks. His mother is well, and blood cultures from mother and baby are negative at 48 hours. Results: platelets 48 × 10^3/µL (48 × 10^9/L), fibrinogen 62 mg/dL (0.62 g/L; reference for age 167-399), D-dimer markedly raised, protein C activity below 1% (reference for term infants in the first days of life 17-53%), antithrombin 51% (reference for age 39-87%). Both parents are healthy, and each has a protein C activity of about 50% (adult reference 70-140%). The most likely diagnosis is:

Severe inherited protein C deficiency

Physiologically low newborn protein C

Heterozygous protein C deficiency

Sepsis-induced disseminated intravascular coagulation

Factor V Leiden increases the risk of venous thrombosis because its factor Va:

Resists cleavage by activated protein C

Is produced in excess by the liver

Blocks the action of antithrombin

Binds factor Xa much more strongly

Disease states: hypercoagulable states

6 ASCP MLS practice questions on Disease states: hypercoagulable states, part of Hematology. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A term boy is well at birth, but at 30 hours he develops spreading purple-black skin lesions on his legs and buttocks. His mother is well, and blood cultures from mother and baby are negative at 48 hours. Results: platelets 48 × 10^3/µL (48 × 10^9/L), fibrinogen 62 mg/dL (0.62 g/L; reference for age 167-399), D-dimer markedly raised, protein C activity below 1% (reference for term infants in the first days of life 17-53%), antithrombin 51% (reference for age 39-87%). Both parents are healthy, and each has a protein C activity of about 50% (adult reference 70-140%). The most likely diagnosis is:
1. APhysiologically low newborn protein C
2. BSevere inherited protein C deficiency
3. CHeterozygous protein C deficiency
4. DSepsis-induced disseminated intravascular coagulation
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Answer: B · Severe inherited protein C deficiency
Purpura fulminans in the first days of life with undetectable protein C is the classic picture of homozygous or compound heterozygous protein C deficiency. Newborns normally have low protein C, but not below 1%, and physiologic levels do not cause skin necrosis. Each parent has about half the normal adult level, which marks them as heterozygous carriers who have each passed on one defective gene. DIC can lower protein C, but negative cultures and the parents' results point to an inherited cause, and the low platelets and fibrinogen follow from the clotting. Treatment is protein C concentrate or plasma, and genetic testing confirms the defect.
- A: Normal newborn protein C is low but not below 1%, and it does not cause purpura fulminans.
- C: A heterozygous baby would have about half the newborn level, not an undetectable one.
- D: Cultures are negative, and the parents' carrier levels point to an inherited cause.
Question 2 · Hard
A 26-year-old woman taking an oral contraceptive has a cerebral venous sinus thrombosis. APC resistance, protein C, protein S and antithrombin are all normal. Which inherited variant is genotyping most likely to find?
1. AProthrombin G20210A
2. BMTHFR C677T
3. CJAK2 V617F
4. DFactor V Leiden
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Answer: A · Prothrombin G20210A
Prothrombin G20210A is a change in the 3' untranslated region of the prothrombin gene that raises prothrombin levels by about 30%. It is the second most common inherited thrombophilia, carried by about 2% of people of European descent, and it adds to the clotting risk of estrogen, including cerebral vein thrombosis. Prothrombin activity overlaps the normal range, so the variant is found only by DNA testing. Functional tests such as APC resistance, protein C, protein S and antithrombin cannot detect it.
- B: MTHFR C677T is common but is not a meaningful thrombophilia, and testing is not advised.
- C: JAK2 V617F is acquired, not inherited, and points to a myeloproliferative neoplasm.
- D: A normal APC resistance test makes factor V Leiden very unlikely.
Question 3 · Medium
On day 3 of warfarin, started without heparin, a woman develops painful purple lesions on her thighs that turn necrotic. Which inherited thrombophilia is most likely?
1. AProthrombin G20210A
2. BProtein C deficiency
3. CFactor V Leiden
4. DAntithrombin deficiency
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Answer: B · Protein C deficiency
Warfarin lowers all vitamin K-dependent proteins, but protein C has a half-life of only about 8 hours, so it falls faster than prothrombin and factors IX and X. In a person who starts with half-normal protein C, this opens a short hypercoagulable window, and thrombi form in skin venules, causing necrosis. This is why warfarin is started under heparin cover in known protein C deficiency. Protein S deficiency can rarely cause the same picture.
- A: The prothrombin variant raises prothrombin and does not cause this early imbalance.
- C: Factor V Leiden alters factor V, which warfarin does not affect.
- D: Antithrombin is not vitamin K-dependent, so warfarin does not lower it.
Question 4 · Easy
Factor V Leiden increases the risk of venous thrombosis because its factor Va:
1. AResists cleavage by activated protein C
2. BIs produced in excess by the liver
3. CBlocks the action of antithrombin
4. DBinds factor Xa much more strongly
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Answer: A · Resists cleavage by activated protein C
Factor V Leiden is a single amino acid change (Arg506Gln) at one of the sites where activated protein C cuts factor Va. The altered factor Va is inactivated much more slowly, so thrombin generation goes on longer. It is the most common inherited thrombophilia in people of European descent, with about 5% carrying one copy. It is detected with an APC resistance test or by genotyping.
- B: Factor V levels are normal in factor V Leiden.
- C: Antithrombin works normally; the defect is in the protein C pathway.
- D: The mutation slows inactivation by APC; it does not change binding to factor Xa.
Question 5 · Hard
A 31-year-old woman has had three pregnancy losses before 10 weeks and now has a deep vein thrombosis. She has never bled abnormally. Her APTT is 52 s (reference 25-35) and does not correct in an immediate 1:1 mix; the PT is normal. The most likely diagnosis is:
1. AAntiphospholipid syndrome
2. BAcquired hemophilia A
3. CProtein S deficiency
4. DFactor XI deficiency
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Answer: A · Antiphospholipid syndrome
A non-correcting APTT in someone who clots rather than bleeds points to a lupus anticoagulant. Together with recurrent early pregnancy loss and venous thrombosis, this fits antiphospholipid syndrome. The diagnosis needs lupus anticoagulant, anticardiolipin or anti-beta2-glycoprotein I antibodies to be positive on two occasions at least 12 weeks apart. The APTT is prolonged in vitro because the antibodies interfere with the phospholipid in the test reagent.
- B: Acquired hemophilia A causes serious bleeding, not thrombosis.
- C: Protein S deficiency causes thrombosis but does not prolong the APTT.
- D: Factor XI deficiency corrects on mixing and causes bleeding, not clotting.
Question 6 · Medium
Unlike factor V Leiden, which causes mainly venous thrombosis, antiphospholipid syndrome commonly causes:
1. AIsolated superficial thrombophlebitis
2. BVenous thrombosis only in pregnancy
3. CBleeding from the prolonged APTT
4. DArterial as well as venous thrombosis
Answer and explanation in LearnFree account

Disease states: hypercoagulable states

A 26-year-old woman taking an oral contraceptive has a cerebral venous sinus thrombosis. APC resistance, protein C, protein S and antithrombin are all normal. Which inherited variant is genotyping most likely to find?

On day 3 of warfarin, started without heparin, a woman develops painful purple lesions on her thighs that turn necrotic. Which inherited thrombophilia is most likely?

Factor V Leiden increases the risk of venous thrombosis because its factor Va:

A 31-year-old woman has had three pregnancy losses before 10 weeks and now has a deep vein thrombosis. She has never bled abnormally. Her APTT is 52 s (reference 25-35) and does not correct in an immediate 1:1 mix; the PT is normal. The most likely diagnosis is:

Unlike factor V Leiden, which causes mainly venous thrombosis, antiphospholipid syndrome commonly causes: