40-year-old (female) with DVT prophylaxis

00:02 A 40 year old African American female presents to the emergency room with severe left upper quadrant pain, which has a duration of 3 hours, described as stabbing in quality, and rated as 10/10 on the pain scale.

00:18 Physical examination confirms the patient's pain distribution and also, splenomegaly is noted.

00:24 There is a significant past medical history of sickle cell anemia.

00:28 She is admitted to the hospital for close observation and placed on DVT prophylaxis as part of routine protocol.

00:36 Routine blood work later demonstrates a normal PT level but an elevated PTT level.

00:42 Which of the following factors is most directly affected by her DVT prophylaxis? Answer choice (A) - Factor VII Answer choice (B) - factor XIIa Answer choice (C) - factor VIIa Answer choice (D) - factor X Answer choice (E) - factor XII Now take a moment to come to the answer by yourself before we go through it together.

01:12 Okay, let's jump in to this question together.

01:15 The first thing to do is to discuss the question characteristics.

01:19 Now this is a pathology question and this falls to the category of haematology, so Path-Haem.

01:24 Now this is a 2-step question.

01:26 We first have to figure out what DVT prophylaxis that they're administering to the patient.

01:31 And then second, we have to know the mechanism of action along the intrinsic and extrinsic pathways of coagulation to know which factor is involved.

01:42 And the stem is absolutely required in this case because we need the patient's history and an understanding of what the clinical scenario is in which they're giving her DVT prophylaxis.

01:52 Now let's walk through this question together.

01:54 Step 1 - we need to determine which DVT prophylaxis the patient is receiving.

02:00 Now it's very important to know, both clinically as a physician and also for USMLE that heparin is routinely used for DVT prophylaxis in a hospital setting as it has a rapid onset of action and can be discontinued on discharge without long-term effects.

02:17 So in this case, we first have to know, patient is most likely on heparin for DVT prophylaxis.

02:22 Now step 2, we need to determine which clotting factors are most affected by heparin.

02:29 Now we know heparin has major anticoagulation effect by binding to the enzyme inhibitor antithrombin III which in turn inactivates thrombin and activated factor X, thus interfering with the common pathway.

02:45 Now, this patient has a normal PT level which is appropriate since the extrinsic pathway of the coagulation pathway is not affected by heparin.

02:57 But the patient does have a prolonged PTT level which is due to inhibition of the activation of the intrinsic pathway and also the common pathway so we expect.

03:09 So the correct answer in this case is answer choice (D) - factor X.

03:15 Now let's refer to the image that shows the intrinsic and extrinsic pathways of coagulation, extremely important for us to be able to determine why heparin is affecting factor X and also why it's causing an elevated PTT level.

03:31 Let's start first with the right side - the more simple side in my opinion and also the side that's not going to be ever forgotten by a student because the extrinsic pathway is related to the PT level but also it's clinically relevant as it is more simple but factor X is involved in both pathways.

03:55 Now let's start on the right side.

03:58 If we look first, we will see that trauma will cause the conversion of factor VII to VIIa, and then that will cause conversion of factor X to Xa, and then it will enter into what's called the commmon pathway.

04:13 So really the extrinsic pathway as you can see there is extremely simple in really is to the point of some type of extrinsic trauma or tissue trauma causing the conversion of these factors.

04:28 Now let's look over to our intrinsic pathway which will produce our elevated PTT level.

04:34 Now, there we see that some type of damaged surface in the intrinsic pathway will cause factor XII to convert to factor XIIa, then we'll have factor XI convert to factor XIa then IX to IXa, and then we'll have again X to Xa.

04:53 Now the common pathway starts at factor X, as it's converted to Xa.

04:58 But as we can see there on the right side, there is a notation that antithrombin actually prevents this conversion of X to Xa and we know that thrombin which is factor IIa is actually inhibited by heparin.

05:20 So there we see Xa.

05:24 Now prothrombin is converted by Xa to thrombin by factor Xa - into thrombin which is also called factor IIa.

05:34 Now factor IIa being formed is a clotting factor that's in the common pathway.

05:40 Now if we have heparin it's going to inhibit both the conversion of X to Xa so we can't activate factor X, and also inhibits the conversion of prothrombin to thrombin.

05:54 So in two manners there in the common pathway, we see that heparin would prohibit the continuation of this coagulation pathway and also would prevent the activation of both thrombin and activated Xa, and the common pathway is how we are going to have an elevated PTT.

06:20 Next, let's go through some high-yield facts for this question.

06:24 Now in patients that have sickle cell disease, venous thromboembolism is extremely common.

06:31 Now in the inpatient setting, DVT prophylaxis is routinely given as a form of subcutaneous heparin .

06:38 That's extremely important to know the route of administration.

06:42 It is not IV heparin, it is subcu heparin usually administered twice a day, sometimes three times a day depending on the ongoing condition of the patient.

06:52 And sometimes, they may ask you how much is given, and the answer is 5000 units either twice or three times a day depending on the condition.

07:02 Now heparin has a fast onset of action and a short half-life so it can easily be discontinued in the hospital with no post-discharge effects.

07:11 The patient doesn't have to worry about being at the risk of bleeding once he leaves the hospital, it has a very short half-life, hence the 2-3x a day dosing.

07:20 Now heparin interferes with the common pathway as we described while going through the image by binding to antithrombin III which in turn inactivates thrombin and activated factor X.

07:32 Now heparin we now know and have discussed prolongs PTT which is a measure of function of the intrinsic and also the common pathways.

07:43 Very important to know though, heparin has absolutely no effect on PT level which is a factor of the extrinsic pathway.