Hdb Blood Final Cram Flashcards

Front 1

What factors are deficient in vit K deficiency?

Back 1

II, VII, IX, X, protein C, protein S

Front 2

What does antithrombin do and what activates it?

Back 2

Inhibits thrombin and factors VIIa, IXa, Xa, XIa, and XIIa. Activated by heparin

Front 3

What are some natural inhibitors of coagulation released by surrounding endothelium? Natural promoter of aggregation?

Back 3

Nitric Oxide (NO) from ECs and plts inhibits platelet aggregation and promotes vasodilation.

Prostacyclin synthesized by ECs and inhibits platelet aggregation and promotes vasodilation.

Pro-aggregator = thromboxane A2

Front 4

Whats clopidogrel?

Back 4

Plavix. Blocks ADP binding to platelet P2Y1,12 and prevents aggregation. Anticoagulant.

Front 5

How does aspirin work?

Back 5

irreversibly inhibits or decreases cyclooxegenase (COX) activity, decreasing thromboxane A2 synthesis. Anticoagulant. Ibuprofen does the same thing but mechanism is reversible.

Front 6

Name the major classes of PLATELET inhibitors.

Back 6

Anti-ADP, block ADP platelet receptors (clopidogrel).
COX inhibitors
IIb/IIIa inhibitors
Increasing plt cAMP (dipyrimadole)

Front 7

Name categories of platelet pathology

Back 7

Low platelets (mucosal bleeding). Abnormal platelets. Too many platelets (thrombosis

Front 8

Differentiate clinical findings of factor and platelet deficiencies.

Back 8

Platelet deficiency: petechiae, superficial ecchymosis, persistent oozing, equal M/F, rarely a family history of bleeding.

Factor deficiency: No petechiae, large and deep ecchymoses, delayed bleeds common, superficial bleeds uncommon, 90% males (hemophilia), FH component common

Front 9

What does the bleeding time test tell you?

Back 9

Is prolonged if platelets are decreased or qualitatively abnormal. Not extremely accurate but if abnormal think PLATELET problem, not factors.

Front 10

Whats a platelet aggregation test?

Back 10

Test ability of platelets to aggregate with various agonists applied.

Front 11

What is ristocetin? how is it used clinically?

Back 11

First used as an AB, no longer since caused platelet aggregation. Platelet binding directly related to amount of vWF bound to platelet. If ristocetin aggregation test is abnormal (ie plts don't aggregate in its presence) you have either a deficiency of vWF (vWF disease), or inability of plts to bind vWF (Bernard Soulier Syndrome, no GpIb)

Front 12

What is hereditary hemmorhagic telangiectasia?

Back 12

Dilated microvasculature lesions of mucosal surfaces in CNS, lungs. caused by genetic defect of endoglin, part of the endothelium. AD inheritance.

common sx = epistaxis, GI bleeds. iron deficiency possible.
tx = estrogen, laser, embolization

Front 13

Ehlers-Danlos syndrome?

Back 13

CT disorder present with increased bruising/purpora from abnormal platelet/CT interaction. May heal poorly and have hyperextensibility.

Front 14

What are causes of ACQUIRED vascular defects?

Back 14

Senile purpora - atrophy of collagen
Scurvy - vit C deficiency causing collagen defects (see bleeding around hair follicles)
Steroids - weakening of supportive CT

Front 15

What are qualitative platelet defects and what causes them?

Back 15

Disorders of platelet function. Abnormal bleeding and aggregation tests in presence of normal plt count. Mucosal bleeding is highly suspicious of this. Hereditary causes rare, more common secondary to certain drugs.

Can affect adhesion (GPIb, a probs), aggregation (GPIIa/IIB probs), or activation (ADP binding, thromboxane, thrombin, deficient granules, list goes on)

Front 16

details of bernard-soulier syndrome

Back 16

AR inheritance.
Defect in GpIb which binds vWF. Will not aggregate with ristocetin but will with all others. Presents in childhood with nosebleeds, mucosal bleeding. BT prolonged, vWF level is normal.

Tx = plt transfusion

Front 17

details of Glanzmann's Thromasthenia

Back 17

Rare, AR inheritance.
GpIIa/GpIIIb mutation, interferes with aggregation and fibrinogen binding. Platelets aggregate only with ristocetin, none of the others. BT prolonged. Presents in childhood with mucocutaneous bleeding.

Tx = plt transfusion

Front 18

What are storage pool disorders?

Back 18

Platelet condition where granules are low or nonexistent. On BT don't get secondary peak that indicates further aggregation resulting from granule release.

Front 19

What causes most qualitative bleeding disorders?

Back 19

anticoagulant drugs like clopidogrel and aspirin as well as medical diseases like renal failure. Tx by withholding drug, treating illness, or giving plts if nec.

Front 20

What are some inherited and acquired causes of thrombocytopenia?

Back 20

Inherited is rare: thrombopoietin mutation, may heggelin anomaly (giant plts, usually asymptomatic), wiskott-aldrich syndrome

Acquired: infiltrative BM disease ie cancer, viral infection (HIV, hepatitis), drugs (chemo, etoh), nutritional deficiency

Front 21

What is ITP?

Back 21

Idiopathic (autoimmune) thrombocytopenic purpura. Circulating IgG against GPIIa/IIIb usually. Very low plt count. increased megakaryocytes in BM. other blood normal. may be caused by infection, IBD, collagen vascular disease, lymphoma.

tx: steroids help 80%, gammaglobin infusions compete with spleen macrophages, splenectomy. Rituximab is new drug, anti-b cell.

New evidence shows megakaryocytes may be targeted by ABs as well.

Front 22

Drug induced Thrombocytopenia

Back 22

quinine-quinidine, heparin. induce antibodies. withdraw drug. with heparin give alternative anticoag.

Front 23

Thrombotic Thrombocytopenic Purpura (TTP)

Back 23

Caused by deficiency of (or inhibition via drugs/autoantibody) ADAMTS14 a Mettaloprotease that cleaves vWF multimers. Causes platelet adherence and plt thrombi.

Sx: fever, thrombocytopenia, small vessel occlusion of kidney and cns, microangiopathic hemolytic anemia.

SCHISTOCYTES. lab values consistent with hemolytic anemia (high LDH, retic count, tbili, decrease haptolobin). coag tests normal.

Tx: replace enzyme (via FFP) or decrease antibody (plasmapheresis)

Front 24

Hemolytic Uremic Syndrome (HUS)

Back 24

Symptoms of hemolytic anemia, renal failure. Schistocytes present, ADAMST normal. Can be associated with e.coli or shigella infection. may require temporary dialysis

Front 25

Differences of PT and aPTT?

Back 25

Prothrombin time (PT) is a measure of extrinsic and common pathways. It is sensitive to VII, V, X, prothrombin, thrombin, fibrinogen.

activated Partial Thromboplastin Time (aPTT) measures intrinsic and common pathways.

Front 26

What do mixing studies tell you?

Back 26

If mix patient's plasma and normal plasma and still prolonged, an inhibitor of a factor is present. If normalizes, then a factor is deficient.

Front 27

Hemophilia A and B?

Back 27

A = factor VIII deficiency (1/10,000 males), B = factor IX deficiency at birth (1/20,000 males). X-linked. spontaneous mutation in hem A possible, happens 20% time.

In hemophilia A first intron disease discovered (intron 22 defect, inversion causes 56% cases). Missense mutation in most mild cases.

clinical manifestations = hemarthrosis, hematomas, intracranial bleeds, other bleeding at mouth, gi tract, kidney

Front 28

Coag factor deficiency classification scheme?

Back 28

severe: factor >1% of normal, sustain spontaneous hemmorhage.
moderate: factor of 1-5% normal.
Mild: Factor >5% normal, bleed only with surgery or trauma

Front 29

hemophilia treatment?

Back 29

Factor replacement therapy in severe cases. Side effects of allergy and antibody development.

For mild cases consider factor VIII, not IX. Desmopressin.

fibrinolysis inhibitors - AMICAR

nowadays prophylactic factor replacement.

model for gene therapy.

Front 30

What is special about factor XII deficiency?

Back 30

Patients don't bleed. PTT prolonged and may have thrombolysis.

Front 31

What's in cryoprecipitate?

Back 31

cold insoluble plasma proteins. vWF, factors VIII, XIII, fibrinogen, fibronectin.

Front 32

Where is vWF made?

Back 32

endothelial cells and megakaryocytes.carries factor VIII.

Front 33

What are different types of vWF disease?

Back 33

Quantitative: Type 1 (mild-moderate, most common), type 3 (severe)

Qualitative: loss of function, gain of function, mutation in FVIII binding (all different type 2s)

Remember in vWD you have reduced aPTT due to decreased FVIII that vWF carries.

Front 34

what is most common bleeding disorder?

Back 34

vWD type 1. Autosomal dominant.

Front 35

What does liver damage cause in terms of coagulation/

Back 35

Decreased clotting factors, low plts, causing oozing and bleeding. vit K dependent factor particulary affected, especially VII. decreased fibrinogen, incr factor consumption, fibrinolysis activation.

prolonged PTT and PT. enlarged spleen low platelets.

tx: FFP, platelets, cryoprecipitate?

Front 36

Pathophys of DIC

Back 36

pathologic activation of coagulation by an underlying disease process leading to fibrin clot formation and secondary fibrinolysis which consumes factors, platelets, red cells. May manifest as thrombosis, bleeding, or both. The fulminant syndrome is life threatening.Thrombosis of small and medium size vessels leads to organ failure.

Key mediator is tissue factor from damaged endothelium or due to pro-inflammatory cytokines TNF, IL1, endotoxin. Massive thrombin activation. Fibrinolysis also activated, leading to fibrin degradation products.

oozing and bleeding.

Tx: TREAT UNDERLYING DISORDER. Replace factors AND platelets.

Front 37

What are the acquired coagulation disorders?

Back 37

Liver disease, vit K deficiency, DIC, acquired inhibitor antibodies to FVIII.

Front 38

What is Virchow's Triad (risk factors for arterial and venous thrombosis)?

Back 38

Endothelial injury, abnormal blood flow, hypercoagulability. In arterial, vascular injury important. In venous, hypercoag and stasis important.

Front 39

Characteristics of arterial clot

Back 39

damaged endothelium usually ie artherosclerotic plaque. "White thrombus". PDGF stimulates migration and proliferation of smooth muscle cells and fibroblasts in the intima of artery. Vessel wall thickens. Emboli of platelets/fibrin can lead to TIA or limb gangrene.

Front 40

Risk factors for arterial thrombosis

Back 40

FH, hyperlipids, male gender, diabetes, tobacco, elevated factors, HTN, age

occur mostly in elderly. usually vascular not hematological.

tx with antiplatelets, anticoags, tx of medical conditions

Front 41

Characteristics of venous clot

Back 41

Stasis and hypercoagulability important. "Red thrombus" due to stasis, platelet incorporate RBCs. Can propogate, resolve, embolize, recanalize.

Front 42

Whats a DVT foo?

Back 42

Deep vein thrombosis. mostly in legs, can occur in arms and lungs. Can also be superficial, deep more dangerous (greater risk of pulmonary embolism).

swelling, redness, pain. Doppler for dx.

RFs = immobilization, obesity, cancer, surgery

plasma d-dimer is breakdown product of crosslinked fibrin, negative predictive value (if negative, pt prob doesn't have DVT).

Front 43

RFs for PE

Back 43

prolonged bed rest, surgery especially orthopedic, BCP, cancer, pregnancy, crushing trauma, airplanes

Front 44

What are natural inhibitors of coagulation?

Back 44

Antithrombin inhibits serine proteases including thrombin.
protein C and S . inhibit factors VIIIa and Va.
Tissue Factor Pathway Inhibitor (TFPI) binds Xa and VIIa-TF complex

Front 45

What is fibrinolysis?

Back 45

Degradation of fibrin clots by PLASMIN. tissue plasminogen activator (tPA) converts plasminogen to plasmin forming D-dimer (DVT !) and FDPs.

Front 46

What is factor V leiden mutation?

Back 46

Factor V can't be inactivated, leads to hypercoagulable state. found more in caucasians. can't be inactivated by prot C. single pt mutation. COMMON. Homozygotes at much higher VTE risk. Does not increase risk of arterial thrombosis.

Front 47

describe familial thrombophilia

Back 47

hereditary condition of too much coagulation (thrombophilia). Causes venous thrombo embolism.

Front 48

Examples of inherited deficiencies of coagulation inhibitors?

Back 48

Protein C, S, antithrombin. AD transmission. Higher risk of VTE than favtor V mutation .

Front 49

What are the main acquired thrombophilic disorders?

Back 49

Antiphospholipid antibodies, malignancy, myeloproliferative disorders, nephrotic syndrome, PNH, drugs, BCPs

Front 50

Whats APS?

Back 50

Antiphospholipid syndrome. IgG to plasma protein antigens, causing venous and arterial thrombosis. recurrent fetal loss due to microthrombi. Can be associated with lupus. Prolonged PT or PTT but has thrombosis not bleeding!

Front 51

What does heparin do?

Back 51

Potentiates antithrombin effects by helping it bind and inactivate thrombin, IXa, XIa, Xa. Infused not good oral bioavailability. binds many plasma proteins, dose carefully.

long chain heparin necessary to inhibit thrombin, not necessary to inhibit Xa. Unfractioned heparin not often given for treatment, usually as prophylaxis.

side effect is bleeding. can give protamine to reverse effects.>2months increases osteoporosis risk.

heparin induced thrombocytopenia in 5% cases. thrombosis due to autoimmune response.

Front 52

What is LMWH?

Back 52

low molecule weight heparin. given subQ not IV. Xa > AT. less platelet interaction than heparin. doesnt bind plasma proteins. LONGER half life. HIT much lower. no antidote, protamine doesnt really work

Front 53

Factor Xa inhibitors?

Back 53

Xa activates thrombin from prothrombin, II to IIa. Drug called Fondaparinux. AT cofactor inactivates Xa. Prophylactic and tx of DVT. no antidote.

Front 54

If pt has HIT what can you give?

Back 54

Direct thrombin/Xa inhibitors like argatroban, lepirudin, bivalrudin. not used frequently. Could also use indirect Xa inhibitors

Front 55

Most common oral anticoagulant?

Back 55

Warfarin (Coumadin). long half life of 36-48hrs. inhibits vit k dependent factors. takes 3-5 days to take effect. narrow therapeutic window. Affects VII most, so monitor with PT not PTT like heparin. Keep INR between 2-3.

side effects of bleeding, skin necrosis. vit k antidote.

Front 56

how calculate INR?

Back 56

patient PT over control PT raised to ISI

Front 57

basics of treating venous clot?

Back 57

LMWH or UFH for 5 days with warfarin. hep continued until INR >2. Antiplatelets NOT useful

Front 58

basics of treating arterial clot?

Back 58

heparin, ASA, and or coumadin. tPA used acutely as in heart attack. Clopidogrel used with stents.

Front 59

how do you calclulate the corrected count increment?

Back 59

This is used post platelet transfusion to see if recipient body is accepting platelets. Equation is CCI = ((Post Tx Plt - Pre Tx Plt)/# plts transfused) * BSA. Expect >7500 within an hr and >5000 in 24hrs.

Front 60

What are some reasons/risk factors for failed plt transfusion?

Back 60

Pt factors: multiple transfusion, male, multiparity, alloimmunization.

clinical factors: fever, sepsis, splenomegaly, clinical bleeding, rbc transfusion, DIC, TTP, neutropenia

blood bank factors: ABO match, storage time, HLA match

Front 61

how do you reduce risk of alloimmunization?

Back 61

Decrease leukocytes in transfusion product, these typically contain the antigens that donor APCs will present to recipient Tcells. (TRAP study showed that reducing leukocytes in product does reduce incidence of alloimmunization).

Front 62

What is platelet cross matching?

Back 62

assay to determine if donor platelets and patient plasma interact via antibodies to avoid this occuring in the pt.

Front 63

Concerning side effect of platelet transfusion?

Back 63

Transfusion related acute lung injure (TRALI), much higher incidence post-platelet transfusion than RBC transfusion. Some studies suggest no improved outcome due to platelet transfusion in terms of bleeding but increased TRALI incidence.