Setting: office
CC: “I took aspirin, and when I cut myself shaving I bled for 2 days!”
VS: normal
HPI: A 23-year-old woman who is generally healthy comes to your office because of abnormal bleeding after a minor cut. It stood out because she usually never takes aspirin, but this time after using aspirin for a headache, the skin kept oozing blood for more than 2 days.
PMHX: prolonged bleeding after dental extraction in past
Medications: none
PE:
Skin: bleeding from skin nick/cut when shaving; some petechiae of lower extremities
Initial Orders:
CBC
PT and aPTT
CHEM-7
LFTs
Move the clock forward until the time that says “Report Available” for the CBC, PT, and aPTT. All bleeding problems need at least these tests. LFTs are done because most clotting factors are made in the liver.
Which of these is not made in the liver?
a. Factor VIII and vWF
b. Factor IX and X
c. Fibrinogen
d. Factor II, VII
e. Albumin
Answer a. Factor VIII and vWF
Factor VIII and vWF are made under the endothelial cell lining of the vasculature. That is precisely where they are needed when a person is cut and that is where they are both made and stored. All of the other clotting factors are made in the liver. That is why the PT and aPTT tell more about liver function than the transaminases AST and ALT. You can damage a tiny part of the liver (<5%) and have a huge bump up in AST/ALT levels, but you need to damage 70% to 80% of the liver before you even begin to see a synthetic abnormality of the clotting factors.
Platelet-Related Bleeding
• Skin–petechiae
• Nasal–epistaxis
• Gums and gingiva
• Vaginal
Factor-Related Bleeding
• Joints–hemarthrosis
• Muscles and hematoma
Move the clock 30 to 60 minutes to get the stat laboratory test report.
CBC: hematocrit 38%; MCV 88 fL; WBCs 8000/μL; platelets 225,000/μL (normal)
PT: 12 seconds (normal)
aPTT: 70 seconds (abnormally prolonged)
Chemistry and LFTs: normal; normal LDH
Causes of prolonged aPTT
• Deficiency of factor VIII, IX, XI, XII
• Acquired inhibitors of these factors
• von Willebrand disease (vWD)
• Antiphospholipid syndromes
Why can this not be hemophilia A?
a. Would not present first at this age
b. Wrong type of bleeding
c. Expressed only in men
d. All of the above
Answer d. All of the above
Hemophilia A should present as delayed bleeding into a joint in a male child.
Hemophilia A is an X-linked recessive disorder:
• Men only
• Y chromosome does not count
• Homozygous females are rare
The patient’s bleeding stops. You send her home. The “bleeding time” test is not necessary. You already know she has prolonged bleeding. Also, the bleeding time test is too nonspecific to be useful. Any platelet disorder will give a prolonged bleeding time.
Orders:
vWF antigen level
vWF activity (ristocetin cofactor and collagen activity) level
vWD is autosomally transmitted, either dominant or recessive based on subtype.
Which cell in marrow makes VWF?
a. Neutrophils
b. RBCs
c. Megakaryocytes
d. Lymphocytes
Answer c. Megakaryocytes
Besides endothelial cells and the connective tissue of the vessel wall, vWF is also made by megakaryocytes.
Why is the aPTT level increased in vWD?
a. vWF is in the clotting cascade.
b. Factor VIII is bound to vWF.
c. vWD has an antiphospholipid antibody.
Answer b. Factor VIII is bound to vWF.
When vWF level is decreased, it is not there to bind factor VIII. This elevates the aPTT, but the function of factor VIII, which is a coagulant factor (the antihemophilic factor A), is not impaired. The other name for vWF is “factor VIII antigen.” You should expect to see an elevated aPTT in half of patients with vWD.
The vWF antigen level is low. The ristocetin cofactor activity level is markedly impaired. You repeat the test the patient off aspirin and it persists. There is no active bleeding. This is likely type I vWD, which is seen in about 80% of cases. The patient needs her wisdom teeth removed. You are planning to give desmopressin acetate (DDAVP) or desmopressin prior to the procedure.
What is the mechanism of DDAVP?
a. Increased production of vWF
b. Increased expression of vWF receptors
c. Inhibition of ADAMTS 13
d. Release of subendothelial stores of vWF and factor VIII
e. Inhibition of plasmin
Answer d. Release of subendothelial stores of vWF and factor VIII
DDAVP releases what has already been made under endothelial stores. Aminocaproic acid and tranexamic acid work by inhibiting plasmin.
Type I vWD is a deficiency of vWF or antigen.
vWF acts in two ways:
1. Platelet to platelet IIb/IIIa (aggregation)
2. Platelet to vessel wall Ib/IX (adherence)
DDAVP is given and the dental extraction is performed. Bleeding persists and a subsequent dose of DDAVP is ineffective.
At this point, what medication should you use?
a. Aminocaproic acid
b. Factor VIII replacement
c. Protamine sulfate
d. Steroids
Answer b. Factor VIII replacement
Factor VIII and vWF (antigen) travel bound together. That is why you can use DDAVP for hemophilia treatment and you can use factor VIII replacement of vWD. Thrombin splits factor VIII off vWF. Aminocaproic acid is a plasmin inhibitor of marginal value. Protamine reverses heparin.
Type I vWD is autosomal dominant–half of children inheriting the gene mutation will be affected.
After giving factor VIII replacement, the bleeding stops. Counsel the patient not to use aspirin or aspirin-containing products. Advance the clock until you get the “Case will end in 5 minutes of real time” screen. No additional orders are necessary.