Setting: office
CC: “I have bleeding from my nose.”
HPI: A 32-year-old woman with epistaxis for the past few days visits your office. The patient says she has a lifelong history of bleeding, but cannot remember precisely what the problem is that she bleeds from. She says “they always give me some pills for a week and it all gets better.” She has some “dark spots” on her legs as well. Her menstrual periods can be very heavy at times.
Medications: none regularly
PE:
General: healthy appearing
HEENT: moderate epistaxis
Skin: petechiae on bother lower extremities
Initial Orders: (done stat)
CBC
Prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR)
Many offices and large practices have the ability to do laboratory tests on-site and can order the tests and request immediate results. On CCS, if you are uncertain what you can order, just place the order and the program will tell you if there is anything else you must do to get the results.
Report Available:
CBC: platelet count 27,000/μL
PT, aPTT, INR: all normal
Patients who are unstable can be sent to the hospital ED. You can order initial tests and treatments from the office and then send the person to the higher level of care.
You move this patient to the ED of the hospital. Every time you move a patient, all the original orders go with them unless you specifically stop them. In the ED, orders are:
Repeat CBC
PT, aPTT, INR
Prednisone
Abdominal ultrasound
Hematology evaluation
As you advance the clock, the laboratory test results return:
CBC: platelets: 22,000/μL; hematocrit 40%
PT, aPTT, INR: all normal
Abdominal ultrasound: normal spleen size
Hematology evaluation: “Your patient has been seen. We have no specific recommendations. Please order any tests or treatments you feel are indicated.”
Prednisone decreases the affinity of macrophages for platelets.
Antiplatelet antibodies are too nonspecific to be worthwhile.
One hour after transfer to the ED, the patient’s bleeding worsens. There is melena, more petechiae, and hematuria. A repeat CBC shows platelet level at 8000/μL.
Which is the fastest way to raise the platelet count in idiopathic thrombocytopenic purpura (ITP)?
a. Prednisone
b. Dexamethasone
e. Platelet transfusion
d. IVIG
e. Romiplostim or eltrombopag
Answer d. IVIG
IVIG works faster than any other method of increasing the platelet count and is more effective. Steroids work by inhibiting the affinity of the macrophage for the Fc end of the antibodies attached to platelets. Platelet transfusions do not work because as soon as the platelets enter the body, they are covered with antiplatelet antibodies and rapidly destroyed.
What is the mechanism of IVIG in increasing platelet count?
a. Inhibition of neutrophils
b. Stimulation of megakaryocyte growth
c. Supersaturation of Fc receptors on macrophages
d. Inhibition of leukotrienes
e. Inhibition of interleukin
Answer c. Supersaturation of Fc receptors on macrophages
Antiplatelet antibodies cover the surface of platelets. Macrophages attach to the Fc receptor and “grab” the platelets and bring them to the spleen for destruction.
Megakaryocytes are produced in very high amounts in ITP.
No test can diagnose ITP. Bone marrow is sometimes evaluated to exclude a production problem by finding large numbers of megakaryocytes.
IVIG is ordered. Move the clock forward 1 to 2 hours and recheck the platelet count. If there is severe, life-threatening bleeding 6 hours after the start of steroids and IVIG, you may have to consider platelet transfusion. Platelet transfusion is rarely done for three reasons:
1. Bleeding is rarely severe enough to need platelets.
2. Steroids are usually quite efficacious, starting within hours.
3. Platelets are consumed as soon as you infuse them into the patient.
No one knows why ITP occurs.
New platelets have an increased size or “mean platelet volume.”
As you move the clock forward, the platelet count stabilizes. If this problem recurs, send the patient for evaluation for splenectomy. If you move the clock forward, and ITP recurs after removing the spleen, start romiplostim or eltrombopag.
What is the precise location of platelet destruction in ITP?
a. Intravascular
b. Spleen
c. Kupffer cells of liver
d. Tissue
Answer b. Spleen
After being covered with antiplatelet antibodies and grabbed by macrophages, the platelets are actually destroyed in the spleen. This is why splenectomy is so effective in controlling ITP.
No Spleen = No Platelet Removal
Rh0(D) immune globulin (RhoGAM) or anti-D antibodies have nothing to do with platelets. They stuff up the macrophages.
Romiplostim and eltrombopag are thrombopoietin. They stimulate megakaryocyte growth.
Rituximab removes CD20 lymphocytes, which make antibodies against platelets.
ITP cases end when the platelet counts start to rise and bleeding stops. The platelet count does not have to increase to normal levels. It just has to start rising. Steroids for initial therapy and adding IVIG for life-threatening bleeding remain the standard of care. The most likely fundamental of the basic science question on the Step 3 examination for ITP will be to know the mechanism of how IVIG works. The fragment antigen binding (Fab) end of IVIG has nothing to do with platelets. IVIG mechanism is involved entirely with blocking the macrophage. If the macrophage is fully saturated with Fc ends of IVIG or RhO(D) immune globulin (RhoGAM) (anti-D antibodies), there is no room to bind the Fc ends of the immunoglobulins attached to platelets.
Rituximab works by removing the lymphocytes that make the antibodies that attack platelets. You know that rituximab removes CD20-positive lymphocytes. This is the same mechanism for how it works in cold agglutinin disease and how it works in rheumatoid arthritis.
Romiplostim and eltrombopag are stimulants of megakaryocytes. They are thrombopoietin. These medications are used when splenectomy does not control the disease. It seems that ITP is not entirely a “destruction problem” and that stimulating production seems to help.