von Willebrand’s disease
* the most common inherited coagulopathy caused by a defect in von Willebrand factor, which aids the binding of platelets to collagen
* chromosome 12, autosomal dominant
* Bleeding related to platelets (epistaxis, gingival, gums) with a normal platelet count;
* exacerbated by the use of aspirin
* it is a protective carrier for factor VIII; hence factor VIII may be low and hence aPTT may be elevated (50%)
* low vWF (antigen) level;
* Ristocetin cofactor assay (or vWF activity) – detects vWF dysfunction; deficient ristocetin-induced platelet aggregation
* it means there is no response to ristocetin but this is corrected with the addition of normal plasma
* low factor VIIIc;
* prolonged BT
The combination of a petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity make Von Willebrand’s disease the most likely diagnosis, though hemophilia will be given in the answer choices
DDAVP (desmopressin) if mild, and with vWF concentrate
- autosomal recessive
- disease of platelet adhesion which causes prolonged bleeding times in the presence of normal platelet counts.
- These defective platelets cannot bind to subendothelial collagen properly because of a deficiency or dysfunction of the glycoprotein Ib-IX complex.
- Clinically the patients have impaired hemeostasis and recurrent severe mucosal hemorrhage.
- bleeding out of proportion to the degree of thrombocytopenia
- mild thrombocytopenia, circulating “giant” platelets, severe platelet dysfunction; Hb may be low because of blood loss
- platelets do not aggregate in response to ristocetin, but have a nornal aggregation in response to adenosine diphosphate (ADP), epinephrine and collagen
- The only treatment for an acute episode is a transfusion of normal platelets.
- Cryoprecipitate or vWF concentrate do not help
May–Hegglin anomaly (MHA)
May–Hegglin anomaly (MHA), also known as Dohle leukocyte inclusions with giant platelets and macrothrombocytopenia with leukocyte inclusions
autosomal dominant, MYH9 gene defect (22q12-13)
may found in association with Alport Syndrome
So, look for high frequency hearing loss (82%), proteinuria (40%), cataracts (25%), Hematuria (25%)
platelet glycoprotein IIb/IIIa complex is either deficient or present but dysfunctional leading to defective platelet aggregation and subsequent bleeding
- Platelet counts and other coagulation tests (PT, PTT) are normal
- Prolonged BT
- Primary platelet aggregation response to platelet agonists such as adenosine diphosphate, epinephrine, and collagen is decreased, while the response to ristocetin is normal
May-Hegglin anomaly is rare and not really tested in questions. Also, it is in fact primarily a morphology and quantitative platelet disorder but I put it as a side note to compare.
My way to remember:
- May-Hegglin is Dominant because of Dohle and Giant platelets; remember also Alport is (x-lined) dominant
- Bernard-Soulier has 2 names ADHERED (adhesion problem); so it becomes Giant and do not listen to Ristocetin
- Glanzmann has “G” for AGGreGation and aGree to ristocetin while response to others are decreased
Primary polycythemia/ Polycythemia vera
- a.k.a polycythemia rubra vera; erythremia
- common in age 60 – 75
- overproduction of all three hematopoietic cell lines with predominant elevation in red cell counts
- mutation in the JAK2 protein which regulates marrow production
- red cells grow wildly despite a Low erythropoietin level
- high serum leukocyte alkaline phosphate
- Headache, blurred vision, and tinnitus
- pruritus, especially after hot bath (due to histamine release from increased numbers of basophils)
- HTN, facial plethora, fatigue, Splenomegaly
- Bleeding from engorged blood vessels
- Thrombosis from hyperviscosity
- elevated Hct >60%*
- low MCV and Low iron (because of excessive usage and production)
- however, Vit. B12 levels are elevated for unclear reason
- exclude hypoxia first; normal Oxygen level and *low erythropoietin level in PV
* RCC also has elevated Hct, but the erythropoietin is elevated.
* A small number of patients can convert to AML.
- initial 1st line – Phlebotomy and aspirin prevent thrombosis – target Hct 45%
- Hydroxyurea helps lower the cell count
- indicated in old age >70 years; has thrombosis; has a platelet count >1500; and has cardiovascular risk factors
- Allopurinol or rasburicase protects against uric acid rise
- Interferon alpha may be used in refractory cases
Platelet counts elevate temporarily after spleen removal
Increased erythropoietin level
2° to chronic tissue hypoxia
Kidney cancer is an important differential diagnosis of secondary polycythemia.
Renal Cell Carcinoma is a neoplastic condition that can initially appear with many different paraneoplastic manifestations.
The initial presentation may include hypertension, flank mass, gross or microscopic hematuria, hypercalcemia, fever, weight loss, and/or polycythemia.
Polycythemia may be the presenting sign in 3% of cases of kidney cancer.
Careful evaluation is important in patients presenting with polycythemia and hematuria.
Polycythemia is secondary to a hypersecretion of tumor cytokines, including renin.
The patient’s erythropoietin level is usually high.
Surgical removal of the cancer resolves the polycythemia.
Ferritin = intracelllar storage form of iron.
– closely parrel body stores of iron
So, Ferritin levels are low in IDA but normal to high in anemia of chronic disease
it may be elelvated above normal in ACD because it is an acute phase reactant that is secreted by the liver in inflammatory conditions.
Ref: USMLE secrets
Does anybody aware of the fact that your blood group itself is a minor risk factor for certain type of diseases?
Here it comes –
- Individuals with blood groups A, B, or AB were 5% to 23% more likely to develop coronary heart disease compared with subjects with O blood type, and the associations were not altered by multivariate adjustment of other risk or dietary factors. (The analysis, led by Dr Meian He (Harvard School of Public Health, Boston, MA), included 62 073 women from the Nurses’ Health Study (NHS) and 27 428 men from the Health Professionals Follow-up Study (HPFS) and is published in the September 2012 issue of Arteriosclerosis, Thrombosis, and Vascular Biology.)
- Rotavirus (that causes diarrhea) has certain strains which are more likely to infect people with blood type A.
- People with type B blood have a 72 percent increased risk of pancreatic cancer, and the risk is also elevated for AB blood types (51 percent) and those with blood type A (32 percent) compared to people with blood type O, according to a study published in the Journal of the National Cancer Institute.
- For the women with blood type A and AB seeking fertility treatments—research shows they have more eggs in their ovaries than women with type O blood, who are more likely to have difficulty with fertility treatments.
- People with type A blood appeared to have higher incidences of breast cancer and lung cancer, blood types B and O were more likely to suffer from gastrointestinal cancer, and people with type B and A blood had higher incidents of oral cancer. In general, those with blood type A seemed to have an increases probability of getting cancer, and those with blood type O had a significantly lower risk.
- Patients with blood Group A have a higher chance to develop gastric cancer while those with Group O can easily get Peptic ulcer disease especially duodenal ulcer.
Well, I am group A and all those researches are saying I am more likely to get coronary heart disease, diarrhea and some GI tract cancers than any other blood types! And as you all know, doctors, especially junior doctors, are prone to get gastritis and heart problems because of the nature of the work, stress and duty hours. It shocked me. Since this is a non-modifiable risk factor, all I can do is to reduce the other risk factors such as smoking, heavy drinking, unhealthy eating habit and sedentary life style and finally, of course, to pray.
What about you?