Hypercoagulable State

Update item information
Identifier Hypercoagulable_State_Work_Up
Title Hypercoagulable State
Subject Pathology
Creator Andrew G. Lee, MD, Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, TX; Professor of Ophthalmology, Weill Cornell Medicine; Saira Alex, Baylor College of Medicine Class of 2022
Description Dr. Lee lectures medical students on the hypercoagulable state.
Transcript When talking about the hypercoagulable state, there are two pieces of this hypercoagulable state. One is hyperviscosity, and the other is the coagulation pathway. First, the coagulation pathway, as you know, there's an extrinsic and an intrinsic part of the pathway mediated by factors that are numbered: VII on the extrinsic pathway side; XII, XI, and IX on the intrinsic pathway. They meet at a final common pathway. The final common pathway is mediated by X and V. That leads to a series of activation events where the factors go from V to Va, X to Xa, and the activation converts the prothrombin to the thrombin, the fibrin, fibrinogen, and finally the platelet-thrombin-fibrin complex that allows us to have a clot to seal the bleeding. The reason an ophthalmologist needs to know this is when we encounter stroke in a young person, arterial or vein occlusion in a young person, venous sinus thrombosis, then one of the possible causes is that you are harboring a hypercoagulable state, you have too much coagulation. And now we're going to go through, what are the things we need to know as ophthalmologists when encountering a young patient who has a central vein occlusion. We can have problems with mutations. The mutations can occur at factor V, and the most common is factor V Leiden mutation. You can be heterozygote or homozygote for this mutation and it leads to activated protein C resistance. Or you can have a mutation in the prothrombin gene. A single nucleotide polymorphism A -> G, at position 20210. So, these are the two most common mutations that we see. There is a third mutation that is related to an independent graded risk factor for thrombosis called homocysteine. Homocysteine is converted to the methionine, and so homocysteine is kind of a like a good guy, and methionine is a good guy. This is a folate dependent pathway mediated by an enzyme methylenetetrahydrofolate reductase. Genetic mutations in the methylenetetrahydrofolate reductase at positions 665 and 1286 can lead to increases in homocysteine that's a graded risk factor for thrombosis. So those are the mutations. We can also have deficiency states in the cofactors that allow the clot to be broken down. Those cofactors are protein C and protein S. So, if you have too little of protein C or protein S, you will get a clot. Or the anti-thrombin III which is against the thrombin. So in the deficiency states, anti-thrombin III, protein C, and protein S. In addition, we can have excess of one of the factors: VIII. So, if we have too much VIII or too little protein C, protein S, anti-thrombin III, or if we have mutations in the prothrombin gene, or factor V gene, these all lead to a hypercoagulable state. The other mechanism for getting a blood clot is not from the coagulation pathway but from hyperviscosity: too much cell and not enough liquid. In our blood we can have too many red cells (polycythemia), too many white cells (leukemia, leukocytosis), too many platelets (thrombocythemia, thrombocytosis). We can have too much protein, but not like proteins like albumin, but immunoglobulins. Those can be macroglobulins like lymphoproliferative disorders, like Waldenstrom Macroglobulinemia, or immunoglobulins that attack the endothelium and the protein and the platelet membrane, leading to a platelet thrombin thrombosis. Those antibodies are against the phospholipid, anti-phospholipid antibodies (Lupus anticoagulant). We have functional assays to detect the Lupus anticoagulants and the anticardiolipin antibodies. In our hospital, it's the dilute russel venom viper time, and we are running through PT and PTT. Most places, it's all bundled together so we get all of this. And the endothelial part of it, the glycoprotein IIb antibody. So, these are the antiphospholipid testing. You don't have to Lupus to have Lupus anticoagulant. So, on the hyperviscosity side, we are going to be doing CBC, calcium protein electrophoresis, and testing for the Lupus anticoagulant. So, in any patient who has a thrombosis and is young, think about the hypercoagulable state, the coagulation pathway, hyperviscosities, deficiencies, excesses, and mutations.
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Date 2019-03
Type Image/MovingImage
Format video/mp4
Rights Management Copyright 2019. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E, SLC, UT 84112-5890
Collection Neuro-ophthalmology Virtual Education Library: NOVEL http://NOVEL.utah.edu
Language eng
ARK ark:/87278/s6d550wh
Setname ehsl_novel_lee
Date Created 2019-03-05
Date Modified 2020-01-13
ID 1403717
Reference URL https://collections.lib.utah.edu/ark:/87278/s6d550wh