Heme/Onc Flashcards
Platelet disorder (defect in platelet plug) where you have decreased GpIb.
Bernard-Soulier syndrome
No Gp1b = no platelet adhesion.
Mild thrombocytopenia and Big Suckers (big platelets).
Defect in platelet plug where you have decreased GpIIb/IIIa.
Glanzmann’s Thrombasthenia
Defect in platelet AGGREGATION
On blood smear, you will see no platelet clumping.
Autoimmune issue where the autoantibody will attack GPIIb/IIIa proteins.
Idiopathic thrombocytopnic purpura (seen with SLE at times)
Note: These autoantibodies are made in the spleen and the platelet/antibody complex is consumed in the spleen by splenic macrophages. So, you get DECREASED number of platelets, and INCREASED megakaryocytes.
Also, you see with SLE
Primary platelet disorder in which there is a deficiency of ADAMTS 13 due to autoimmune destruction. ADAMTS 13 is a vWF metalloprotease:
TTP (Thombotic thrombocytpenic purpura).
*Decreased degradation of vWF multimer. Will get increased vWF multimers and therefore increased platelet aggregation and thrombosis, AND DECREASED platelet survival.
Will see SCHISOTOCYTES and neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia.
Treatment: get rid of the autoantibody with plasmaphoresis and corticosteroids.
What casues HUS?
E. Coli H0175H7 tonxin (undercooked beef in children). The toxin damages the GI endothelium causing platelet aggregates, which will cause shearing of RBC’s as they pass by. This looks a lot that TTP (schisotocytes, neurologic and RENAL symptoms, thrombocytopenia, microangiopathic hemolytic anemia).
What will the bleeding time of the primary platelet disorders be? What about PT/PTT?
Bleeding time: increased
PT/PTT: normal–>no problem with the coagulation cascade.
Note: primary platelet issues are Bernard-Soulier syndrome, Glanzmann’s thrombasthenia, ITP, TTP/HUS.
Hemophilia A is an X-linked RECESSIVE (so males get it) deficiency of Factor ?
VIII
Will have increased PTT. (draw out the way that Pathoma did).
Hemophilis B is a deficiency of what clotting factor?
B
Bleeding into deep tissue (blood and joints) and re bleeding after surgical procedures describes what type of problem?
Coagulation cascade problem (as opposed to a problem with primary hemostasis, like platelets).
Remember that platelet problems will present with mucosal bleeding, not deep bleeding.
Vitamin K deficiency causes coagulation cascade problems.
What factors need Vitamin K?
II, VII, IX, X, protein C and protein S
Vitamin K is necessary to gamma carboxylate these factors.
Note: Vitamin K increases PT and PTT.
How does coumadin work?
Blocks Epoxide reductase (which is the made the the liver).
epoxide reductase is the enzyme necessary to activate vitamin K so that it can gamma carboxylate factors II, VII, IX, IX, protein C and protein S.
How can you tell difference between Hemophilia A and an autoantibody against Factor VIII.
Do a mixing study. If you mix good blood with the broken blood of Hemophilia A, it will clot. If there are autoantibodies, it won’t matter.
PTT measures intrinsic or extrinsic pathway.
PTT (XII, XI, IX, VIII)–>intrinsic pathway. HEP works on this pathway to prevent clotting
PT measures intrinsic or extrinsic pathway?
PT (VII)–>extrinsic pathway. Coumadin works on this pathway.
How does liver injury affect coagulation?
Factors are made in liver. So is epoxide reductase, which is necessary to activate vitamin K. So, liver injury decreases coagulation.
Note: Use PT to test for liver issues.
What issue will increase both bleeding time and PTT?
vWB disease.
It is mixed platelet and coagulation disorder.
vWF factor is necessary to stabilize Factor VIII (increase PTT). It is also necessary for platelet adhesion (increased BT).
Diagnosed with RISTOCETIN. If there is a disorder of vWF, there will be NO aggregration upon test.
Treat: Desmopressin: released vWF stored in endothelium (Weibel Palad bodies).
What is DIC?
What is the primary way to diagnose?
Widespread activation of clotting leads to deficiency in clotting factors, which creates a bleeding state.
Caused by something ELSE, like rattlesnake bite, gram - sepsis, trauma, Ob comlicaitons, Pancreatitis, Malignancy, Nephrotic syndrome, transfusion
STOP Make New Thrombi
DX: Increased fibrin split products (D-Dimers)
Increased BT Increased PT Increased PTT Decreased platelets Decreased fibrinogen
There are times when plasmin is activated and it should not be, which creates a clinical picture that looks a lot like DIC because there is an attack on clotting factors and fibrinogen. How do you distinguish the two?
Like DIC, you will have:
Increased PT
Increased PTT
Increased BT
But platelet count will be NORMAL.
And although you will have fibrinOGEN split products, you will NOT HAVE D-DIMERS.
The endothelium produces a molecule called thrombomodulin, which “modulates” thrombin. What exactly does it cause to happen?
Normally thrombin would convert fibrinogen into fibrin, which would stabilize a clot.
Thrombomodulin actually “modulates” thrombin to do something else. It activates Protein C, which will then go and inactivate some of the clotting factors. V and VIII.
What drug do you give a pregnant woman with DVT?
Heparin
Normally, warfarin is what you give to treat DVT, but it is teratogenic, so in pregnant ladies, you give heparin.
Note: Heparin increases Antithrombin III activity.
Drugs that end in dipine are what type of drugs?
Ca2+ channel blockers.
Immotile cilia due to an autosomal recessive mutation in a gene coding for the microtubule associated protein, dyne in.
Male infertility, recurrent sinusitus and bronchiectasis result.
Kartagener Syndrome
Cancer associated with Philadelphia chromosome
t(9:22) BCR-ABL
Chronic myelogenous leukemia
Cancers that down’s patients are most at risk for?
ALL and AML
What virus causes erythematous infectiosum (5th disease)?
Where does this virus replicate?
- Parvo B19 (tiny non-enveloped DNA virus).
2. In bone marrow, because it likes P antigen, which is found on erythrocyte precursors.
Prophylaxis drug for HIV patients with <200 T cell count.
Pentamidine–>to treat Pneumocytstis jiroveci
Heinz bodies, bite bells, microcytic anemia
- What causes it?
G6PD deficiency and oxidative damage of RBCs.
Can be induced by drugs that cause oxidative damage such as TMP-SMX and dapsone (both used as prophylactics in HIV patients with CD 4 < 200.
You are trying to figure out why a girl is having increased mucosal bleeding (gingival bleeding, long periods, etc) because she has iron deficiency anemia.
You do the ristocetin test. What does this tell yo?
Ristocetin is a test that activates GP1b receptors on platelets that bind to vWF on endothelial cells and ultimately cause platelet adhesion. If there is a deficiency of vWF, then the platelet adhesion/aggregation will be deficiency with this test.
Ristocetin tests for vWF.
Reg HbA:
Glutamate (- charged)
HbS, this is the change:
Gluatamate (-)—–>Valine (nonpolar)
HbC, this is the change:
Glutamate (-)—->Lysine (+)
Note: These are all missense mutations!
What will it look like if you have these three side by side on gel electrophoresis?
You will have this:
- HbA +
- HbS +
- HbC +
Why are the cells big in megaloblastic anemia?
No folate or B12, which PREVENTS DNA synthesis. The cells are big because there is not enough DNA to make the cells do their thing (divide and get smaller)
Note: Alcoholism can cause folic acid deficiency.
