Here is the second part of how to master coagulation for the USMLE Step 1. Note, however, that this general theme is applicable to ALL topics for the USMLE Step 1 – since the exam tests students on their understanding of the mechanisms of diseases, and their ability to apply knowledge to novel situations, the students who do best are the ones who invest the time to move beyond memorization.
Here, you will have enough information by the end to answer these two clinically important (and high-yield) questions, while also reviewing some of the most important details of coagulation for the USMLE Step 1.
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1º vs. 2º hemostasis defect – once bleeding stops, which is more likely to restart from the same site? Why does this make sense?
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Using their chemical structure, explain whether heparin or warfarin can be given to pregnant women? Why?
What are the two components of clotting?
Primary hemostasis (platelet plug formation), and secondary hemostasis (coagulation cascade).
What is the purpose of the coagulation cascade?
To stop yourself from bleeding, platelets first aggregate together, but they adhere to each other very weakly. If the platelet plug breaks up again, you will begin bleeding again, so the coagulation cascade produces fibrin cross-links (reinforces) platelets to allow them to bind to each other more strongly, thus decreasing the risk of re-bleeding
What is the hallmark of 1º hemostasis defect?
Mucosal bleeding
Clinical tip: what question can you ask to a patient if you suspect platelet dysfunction?
Do you gums bleed significantly when you brush your teeth?
What is the hallmark of 2º hemostasis defect?
Deep bleeding (e.g. hemarthrosis – bleeding into joints) or prolonged bleeding following tooth extraction
What factor(s) make up the intrinsic pathway?
Factors XII, XI, IX, VIII.
What coagulation study is used to monitor the extrinsic pathway?
Prothrombin time (PT)
The EX(trinsic)-PresidenT went to WAR(farin).
What factor(s) make up the extrinsic pathway?
Damaged endothelium → tissue factor release → Factor VII activation → common pathway activation
What coagulation study is used to monitor the intrinsic pathway?
Partial Thromboplastin Time (PTT)
What comprises the common pathway?
Factor X → Factor V → Factor II (thrombin) → turns fibrinogen → fibrin, which binds platelets more tightly to each other
What is the mechanism of warfarin?
Inhibits the action of vitamin K, which γ-carboxylates glutamate residues on factors II, VII, IX, X as well as protein C + S.
Is warfarin non-polar or polar? Can you give it orally? Why or why not?
Non-polar. Thus, if it is non-polar, it can cross cell membranes (which, as a lipid bilayer, are highly non-polar), meaning it can be absorbed through GI tract.
Thus, warfarin can be given orally.
Is heparin non-polar or polar? Can you give it orally? Why or why not?
Highly polar (because it’s negatively-charged). CanNOT give it orally, since it is highly polar, and thus will not be able to cross the GI tract to be absorbed in your blood.
What test is used to monitor warfarin? Why?
Measure by using PT (prothrombin time).
This is because, at clinically relevant doses => only factor VII affected significantly => normal PTT
What drug? Why?
Used to monitor heparin anticoagulant therapy?
Partial Thromboplastin Time (PTT)Used to monitor what drug?
Warfarin overdose – how do you reverse the effects? Why is this logical?
IV vitamin K* and fresh frozen plasma (FFP)**
*For overdose**Rapid reversal of severe overdose, as will FFP will contain all of the coagulation factors depleted by vitamin K inhibition
Heparin overdose - how do you reverse the effects? Why is this logical?
Protamine sulfate
Recall: heparin is highly negatively charged. Protamine sulfate is highly POSITIVELY charged, so it will bind to heparin and neutralize it.
Heparin-induced thrombocytopenia – what is the mechanism?
Development of IgG antibodies against heparin bound to platelet factor 4 (PF4).
Antibody-heparin-PF4 complex will be eliminated by the immune system (→ thrombocytopenia), and activate activates platelets → thrombosis
Heparin-induced thrombocytopenia – what is the treatment?
Direct thrombin inhibitors (Argatroban, bivalirudin – derived from LEECHES)
Wait!
I strongly recommend that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot. The more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Ready for the answers?
1º vs. 2º hemostasis defect – once bleeding stops, which is more likely to restart from the same site? Why does this make sense?
2º hemostasis deficit more likely to recur
This makes sense, because in a 1º hemostasis defect, you have poor platelet function, but IF you form a platelet plug to stop bleeding, you will have a fully-functional coagulation cascade to reinforce it, forming a STRONG platelet plug. However, if you have a 2º hemostasis defect, you can form a platelet plug well, to stop bleeding, but it will remain weak since the coagulation cascade is defective.
Using their chemical structure, explain whether heparin or warfarin can be given to pregnant women? Why?
Heparin is highly charged, and thus will NOT cross cell membranes, including the placenta.
You DO give heparin to pregnant women.
Do NOT give warfarin to a pregnant woman.
Warfarin = non-polar, so can cross cell membranes/placenta, so COULD reach the baby.
What should you do next?
- Turn the narrative, “Pathogenesis to Presentation” questions into Anki cards by copy/pasting the question/answer into the “Front” and “Back” fields in Anki. Do the same for the fundamental facts that you were unfamiliar with, to maximize your chances of USMLE Step 1 success! Remember: the USMLE is a test of understanding, so the better you can understand these questions, the better your score!
- Add reverse cards when appropriate to your Anki cards
- Re-word the questions/explanations as desired, and BOLD the important text to make it easier to review in the future
- Learn something new? Something unclear? Comment below!
- If you liked this post, please consider sharing it on Facebook/Twitter! I judge the utility of these posts by the number of comments / shares they receive, so if you’d like more, or would like a particular topic addressed, please let us know!
