Episode 036: Hemophilia 101, Pt 1
In this episode, we break down the initial approach to the evaluation of a patient with a suspected bleeding disorder, particularly in regards to hemophilia, including standardized bleeding assessment tools, the basics of the coagulation cascade, and mixing studies.
The first step is taking a thorough bleeding history
The Fellow on Call Bleeding Assessment:
Mucosal bleeding working from nose down: epistaxis (did they need cauterization), gum bleeding, bleeding with tooth pulling, hematochezia, hematuria, menorrhagia or excessive post-partum bleeding
Skin: Bruising, petechiae, telangiectasias
“Ortho bleeding”: spontaneous joint or muscle hematoma
Raises concern for hemophilia
Prior surgical or family history?
Medications?
Always clarify: are these issues lifelong?
The International Society for Thrombosis and Hemostasis scoring tool is useful for standardizing bleeding symptoms, and it can help you determine the likelihood that a patient has an underlying bleeding disorder.
Physical exam
Pay particular attention to:
Assess skin for bruising or petechiae
Assess the fingertips
If having epistaxis, may need to have help to assess nostrils for anatomical issues (vessels)
Assess mucosal surfaces for telangiectasias which could point to a diagnosis of Hereditary Hemorrhagic Telangiectasia, a mimicker of bleeding disorders
Assess thighs and flanks for obvious signs of bruising/bleeding
We sort bleeding disorders into two large buckets
Platelet dysfunction → minor bleeding (i.e., mucosal bleeding, epistaxis)
Factor deficiency → major bleeding (i.e., joint effusions, spontaneous ICH)
The basic workup includes
CBC - to assess for low platelets
Peripheral smear - rule out schistocytes (DIC)
CMP - to check for liver dysfunction or severe renal dysfunction/uremia which leads to platelet dysfunction
PT/INR, aPTT, fibrinogen
Von Willebrand Panel
Coagulation Cascade
PT → measures the extrinsic pathway → factor 7 (lucky)
PTT → measures the intrinsic pathway → factors 12, 11, 9, 8 (TENET)
Intrinsic and extrinsic pathway feed into the common pathway → factors 10, 5, 2, 1 (All dollar bills less than $20)
If a patient has an abnormal PT/PTT, you must ask
Is it a lack of a necessary clotting factor or something interfering with the time it takes a clot to form?
You assess this with a mixing study
A mixing study combines equal parts of the patient’s plasma with control plasma.
Mixing study corrects → deficiency of a coagulation factor
Mixing study does not correct → antibody interfering with assay or the function of the factors in the coagulation cascade
*To correct, the time must be in the normal range for the assay, not just slightly improved!
*The mixing study is assessed at time points 0 hr, 1 hr, 2 hr; the presence of an inhibitory may improve the time initially, but can then become longer again at time points 1hr and/or 2hr
After the mixing study, then you also need to know which of the factors is the issue! How to do this:
Functional assays can be ordered to measure individual coagulation factor function.
Factor 11 – Hemophilia C
Factor 9 – Hemophilia B
Factor 8 – Hemophilia A
Understanding the coagulation cascade allows you know quickly know what to order
References:
https://bleedingscore.certe.nl: ISTH/SCC Bleeding Assessment Tool
https://ashpublications.org/ashclinicalnews/news/2436/How-I-Teach-the-Coagulation-Cascade: “How I Teach the Coagulation Cascade” by Dr. Alice Ma at University of North Carolina
The crew behind the magic:
Show outline: Ronak Mistry
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Vivek Patel
Shownotes, graphics, social media management: Ronak Mistry
