Hematology Flashcards
(97 cards)
1
Q
Outline of events for hemostasis
A
No back to cue card
2
Q
Draw the coagulation cascade
A
cost $ to add a pic, google coagulation cascade
3
Q
What bleeding disorders do PT/INR screen for?
A
- extrinsic pathway factors: VII
- common pathway factors: V, X, prothrombin/thrombin (II), fibrinogen/fibrin
4
Q
What bleeding disorders does PTT screen for?
A
- Intrinsic pathway factors: HMWK, prekallikrein, VIII, IX, XI, XII
- Common pathway factors: II/thrombin, V, X, fibrinogen/fibrin
5
Q
What is thrombin time and when would you expect it to be prolonged?
A
- time required to clot after the addition of thrombin
- may be prolonged in: DIC, hypofibrinogenemia, dysfibrinogenemia
6
Q
What does bleeding time estimate the function of?
A
qualitative platelet function
7
Q
What does a normal INR and an abnormal PTT indicate?
A
deficiency of proximal intrinsic pathway
8
Q
What does an abnormal INR and a normal PTT indicate?
A
Abnormalities of vitamin K dependent factors such as II, VII, IX, and X (1972)
9
Q
What is the mixing test and what does it tell us?
A
- patient’s plasma mixed with normal plasma
- test normalizes = deficiency of a factor
- test does not normalize = inhibitor present
10
Q
What are some minor factor deficiencies?
A
- factor XII deficiency
- defects / deficiency of HMKW kininogen and prekallikrein
- factor XI deficiency
11
Q
What is factor XI deficiency?
A
- autosomal recessive
- causes spontaneous bleeding and then VIII or IW* deficiency
(*thats the what the card reads, but probably should be IX)
12
Q
What are the genetics of hemophilia A?
A
- congenital coagulation disorder resulting from deficiency or abnormality of VIII
- X-linked with +++ different mutations
- up to 30% spontaneous mutations
13
Q
How does hemophilia A present clinically?
A
- onset of bleeding following trauma is usually hours or days after injury since the platelet plug works fine
- bleeding may then persist
- usually present with bleeding into deep tissues or joints as opposed to mucosal bleeding seen with platelet abnormalities
14
Q
What does the lab work look like in hemophilia A?
A
- prolonged PTT
- normal PT/INR
- normal bleeding time
- normal vWF : Ag
15
Q
How is hemophilia A classified?
A
- based on functional levels of VIII
- termed VIII:C
- VIII:Ag refers to the antigenic and not functional levels of VIII
16
Q
What percentage of hemophilia A are severe, moderate, and mild disease?
A
- spontaneous bleeding = < 1%
- severe bleeding = < 2%
- moderate bleeding = 2-5%
- mild bleeding = 5-30%
- no clinical significance = >30%
17
Q
What is the minimal VIII needed for hemostasis?
A
30%
18
Q
What is the treatment for hemophilia A?
A
- DDAVP IV or IN - causes release of stored VIII + vWF from endothelial cells, increased levels in mild to mod dz in prep for minor sx or following trauma
- recombinant VII + plasma-based VIII concentrate - for more serious bleeding
- cryoprecipitate - good enough but not used when specific VIII available
- recombinant fVIIa* - for patients with FVIII inhibitors
(*as written on card, should it be fVIII though?)
19
Q
What are the genetics of hemophilia B?
A
Inherited x-linked deficiency or deficit in IX
20
Q
What does the bloodwork look like in hemophilia B?
A
- increased PTT
- decreased IX
- normal INR/PT
- normal bleeding time
- normal platelet count
- mixing time not resolved (inhibitor of iX present)
21
Q
What is the treatment for hemophilia B?
A
- prothrombin complex concentrate
- pure IX concentrate
22
Q
What is the goal of treatment for hemophilia B?
A
- raise the level to 30% to protect against bleeding post detal extraction or to abort a beginning joint hemarthroses
- raise the level to 50% if major join or IM bleeding is already evident
- rain the level to 100% in life threatening bleeding or before a major operatoin
23
Q
What percentage of activity in hemophilia B is needed for hemostasis?
A
> 30%
24
Q
What is Von Willebrand’s disease?
A
- vWF causes platelet adhesion to collagen, initiating platelet plug formation
- also forms a complex with VIII (acts as a carrier protein) in the blood
25
How is vWF produced?
by endothelial cells + megakaryocytes
26
What are the 3 types of vWF disease?
- type I
- type II
- type III
27
What is type 1 vWF?
- autosomal dominant quantitative deficiency of normally functioning vWF
- abnormal bleeding time
- mild reduction in VIII : C and vWF
28
What is type II vWF?
- variably inherited qualitative deficits in vWF
- dx complicated by many subtypes
- in general, decreased ristocetin assay - measures effectivenss of vWF in agglutinating platelets
29
What is type III vWF?
- autosomal recessive with complete absence of vWF
- severe bleeding
- mucosal bleeding, petechiae, epistaxis, menorrhagia
30
What is the treatment of vWF disease?
- DDAVP - 1 hour prior to surgery, 48 hours b/w injections to allow for VIII + vWF to reaccumulate in endothelial cells, + epsilon-aminocaproic acid or TXA to suppress fibrinolysis, useful in type 1, no value in type II/III
- Humate P - fVIII product which contains high [vWF]
- Cyroprecipitate - 1 bag/10 kg q8-12h x sev days to prevent excessive bleeding after major operation, useful for type I/II/III
31
What is alpha2 antiplasmin deficiency?
homozygote with bleed as severely as a hemophiliac after surgery or trauma
32
What are some acquired bleeding disorders?
- hepatic failure
- renal failure
- thrombocytopenia
- thrombocytopathy
- hypothermia
- vit K deficiency
- warfarin treatment
33
How does liver failure cause bleeding disorders?
- liver = major source of all factors except VIII + vWF
- DDAVP can be used to shorten bleeding times in cirrhotics except in the presence of plt dysfunction or thrombocytopenia
- Lg volumes of FFP may be required to maintain normal factor levels
34
How does renal failure cause bleeding disorders?
- leads to decrease in aggregation + adhesion of plts
| - tx with DDAVP, cryoprecipitate, and conjugated estrogens
35
How does thrombocytopenia cause bleeding disorders?
- failure of production
- splenic sequestration
- consumption
- dilution
- drugs: quinidine, sulfa, oral hypoglycemics, gold, rifampin, mithramycin, heparin
36
How does thrombocytopathy cause bleeding disorders?
- chemo drugs
- thiazides
- alcohol
- estrogen
- antibiotics
- quinidine
- quinine
- methyldopa
- gold
- heparin
- ASA
- NSAIDs
- dextrin
- hypothermia
37
How does hypothermia cause bleeding disorders?
- increased fibrinolytic activity
- thrombocytopathy
- decrease in collagen-induced plt aggregation
- spontaneous bleeding occurs when temp < 30 - 40 degrees C
38
How does vitamin K deficiency cause bleeding disorders?
- necessary for carboxylation of glutamate in factors II, VII, X and IX (1972)
- necessary for carboxylation of protein C and S
- rapidly corrected by FFP
39
How does warfarin treatment cause bleeding disorders?
- effect on protein C and S
- effect on 1972
- reversed by vit K
40
How does bleeding associated with platelet disorders present clinically?
- mucosal bleeding
- easily bruised
- petechiae
- purpura
- menorrhagia
41
What are some platelets disorders?
- Idiopathic (autoimmune) thrombocytopenic purpura
- Glanzmans's Thrombasthenia
- Bernard-Soulier Syndrome
- May-Hegglin Anomaly
- Chediak-Higashi Syndrome
42
What is ITP?
- most common cause of isolated thrombocytopenia
- IgG autoantibody
- plt destroyed in the spleen but the spleen is not usually palpable
- peripheral blood smear shows decreased plts / lg plts
- marrow shows plentiful megakaryocytes
43
How is ITP managed?
- steroids
- spleenectomy (if steroids fail)
- immunosuppressives
- platelets
- plasma exchange
- danazol
- IV gamma globulin
44
What is Glanzman's thrombocytopenia?
- inherited defect of GpIIb/IIIA (plt membrane glycoprotein)
- characterized by impaired plt binding to vWF, fibrinogen, and fibronectin
- leads to severe mucosal bleeding
45
What are the lab findings of Glazman's?
- failure of plts to aggregate with any physiologic agent
- absences of clot retraction
- single plts without aggregates on peripheral blood smear
46
What is the treatment of Glanzman's?
Plt transfusions BUT with develop antibodies , so must be slective when to expose patient to a platelet transfusion
47
What is Bernard-Soulier Syndrome?
- inherited absences of surgace glycoprotein GpIb-IX that binds vWF
- plts don'e adhere + aggregate
- absolute plt #s decrease
- plts larger
48
What is the treatment of Bernard-Soulier Syndrome?
platelet transfusions
49
What are disorders of amplification of plt activation?
- May result from: decreased ADP in dense granules, inability to generate TXA2, inability of platelets to repond normally to TXA2
- Plt aggregation test results found in disorders of plt activation amplification: impaired-to-absent aggregation after exposure to collagen, epi, and low [ADP], normal aggregation after exposure to high [ADP]
- ASA + NSAIDs may produce the same results
50
What is DIC?
- Procoagulant state
- Activation of both coagulation + fibrinolytic systems > thrombin + plasmin in circulation
- Thrombin activates fibrin > fibrin monomers form soluble fibrin clot > microvascular thrombosis > entrapment + depletion of plts
- Simultaneous degradation of these factors by plasmin occurs. Plasmin also degrades V, VIII, IX, XI and activates complement system
- Result = decreased fibrinogen levels + increased degradation product levels
51
DIC diagram
Can't upload picture :(
52
Put simply, what happens in DIC?
- procoagulant activation
- fibrinolytic activation
- inhibitor consumption
- biochemical evidence of end organ damage or failure
53
What are some things associated with DIC?
- complication of obstetrics
- infection & sepsis
- malignancy including leukemia
- shock from any cause
- burns
- crush injuries
- massive transfusion
- liver disease
- hemolysis
- inflammatory and autoimmune conditions
- malignancy hyperthermia
54
What does the lab work look like in DIC?
- decreased plt
- increased PT/INR
- increased PTT
- decreased fibrinogen
- + fibrin monomer present
- high plasma d-dimer and fibrin degradation products
- low levels multiple clotting factors (V and VIII)
- fragmented RBCs on smear
- low thrombin-antithrombin and antithrombin III
- increased coagulation factor degradation fragments (F1,2,FpA)
- decreased plasminogen and alpha2-antiplasmin inhibitors
55
What is the treatment for DIC?
- correct underlying illness
- heparin if treatment of underlying pathology doesn't ameliorate the condition in a few hours
- antithrombin III concentrate
- washed pRBCs
- platelets
- cyropreciptate to replace firbrinogen and VIII
- FFP to replace V, clotting factors, and antithrombin III
- Epsilon-amniocaproic acid (or TXA) to inhibit fibrinolysis, which releases fragments D & E that interfere with normal clot formation
56
What are procoagulant states?
- HIT
- antithrombin III deficiency
- protein C and S deficiencies
- resistance to activated protein C (factor V Leiden)
- lupus anticoagulant
57
What is HIT?
Heparin induced thrombocytopenia
HIT I
- non immune
- normalized with stopping heparin
HIT II
- immune mediated (IgG)
- Ab recognizes multimolecular complex of heparin + plt factor 4 resulting in plt aggregation
58
How do you diagnose HIT II?
- suspect in anyone on heparin who develops thrombosis or when plt < 100
- typically occurs 5-15 days into treatment, sooner if on heparin in past 3 months
- dx: serotonin release assay
59
What are complications resulting from HT II?
- bleeding
- intravascular thrombosis (venous and arterial) with unusual thrombotic complications
- acute plt activation syndromes (fever, flushing)
- skin necrosis
60
How do you manage HIT?
- D/C heparin and wait for it to wear off
OR
- protamine reversal if thrombosis has occurred
- start warfarin under protection of another anticoagulant
61
What are some anticoagulant options for patients with HIT?
- danaproid (25% cross-reactivity)
- ASA (some but limited utility)
- Ancord
- Lepirudin (direct thrombin inhibitor)
- Argatroban
- Dextran
62
Can you switch patients who have HIT to LMWH?
- NO!!!
| - 90% cross-reactivity
63
What is antithrombin III?
- the most important plasma protease inhibitor
| - serine protease inhibitor of thrombin (II), VIIa, IXa, Xa, Xia, and kallilreinin
64
What is antithrombin III deficiency?
- uncommon but significant risk for recurrent, life threatening thrombosis
- most cases apparent before 50 years
- can present with arterial thrombosis
- suspect when patient cannot be adequately anti coagulated with heparin
65
How is antithrombin III deficiency diagnosed?
measure levels and activity
66
What are the causes of antithrombin III deficiency?
- nephrotic syndrome (loss of factor)
- liver disease (site of production)
- malignancy
- malnutrition
- decreased protein production
- DIC
- genetic
67
How do you treat a patient with antithrombin III deficiency requiring anticoagulation?
- antithrombin III concentrates or FFP + heparin
| - followed by oral anticoagulants as per usual
68
When is protein C activated?
- when thrombin binds to endothelial cell R thrombomodulin
| - thrombomodulin brings protein C in proximity to thrombin to be activated
69
What is protein S?
activated protein C co-factor
70
What are the actions of activated protein C / protein S / procoagulant tissue factor?
- inactivates Va and VIIIa > decreased thrombin production
| - inhibits tPA inhibitor (PAI-I) > increased plasminogen activity and increased fibrinolysis
71
What are the causes of protein C deficiency?
- congenital (homozygosity is incompatible with life)
- liver failure
- DIC
- nephrotic syndrome
- inflammatory states
72
How do you diagnose protein C and S deficiency?
- measure protein C levels and activity
| - measure antigen level for protein S
73
What is the management for protein C and S deficiency?
- you only need to treat after thrombosis
- heparin > oral anticoagulants for life - start with low dose warfarin to minimize the transient hypercoaguable state that warfarin induces
74
What is resistance to activated C?
- a common polymorphism of factor V that results in resistance of Va to activated protein C
- present in 1-2% of the population
- most common cause for thrombosis
- associated with increased risk venous thrombus
- indications for long term anticoagulation unknown
75
What is lupus anticoagulant syndrome?
- hypercoagulable state
- present of antiphospholipid antibodies in associated with episodes of thrombosis, recurrent fetal loss, thrombocytopenia, and livedo reticularis
76
How is lupus anticoagulant syndrome diagnosed?
- suspected when PTT increased
- antiphospholipid or anticardiolipin antiboidies detected
- other coagulation tests normal
77
How is lupus anticoagulant syndrome treated?
- anticoagulation during thrombotic events
- warfarin with goal INR > 3.0
- heparin or LMWH for recurrent fetal loss throughout pregnancy
78
What are hematologic drugs?
- protamine
- warfarin
- heparin
- LMWH
- ASA
- Ancord
- EPO
- medicinal leeches
- thrombolytics
79
What is protamine?
- weak anticoagulant
- forms a salt with heparin resulting in loss of anticoagulant activity of both drugs
- used to reverse heparin effects
- too rapid administration can cause hypotension and anaphylactoid reaction
80
What are the common side effects of protamine?
- hypotension
- bradycardia
- pulmonary artery HTN or hypotension
- decreased oxygen consumption
- transitory flushing
- leukopenia
- thrombocytopenia
81
How does warfarin work?
- interferes with prothrombin (II), VII, IX, X, protein C and protein S
- in the liver, these factors are carboxylated in a reaction catabolized by the reduced form of vitamin K
- warfarin prevents the reduction of vitaminK once it has functioned as a cofactor in the carboxylation reaction
82
What are some major complications of warfarin?
- bleeding
| - skin necrosis
83
What is the half-life of warfarin?
- 40 hours
84
What is the reversal agent for warfarin?
- vitamin K
| - FFP
85
What are some common drugs that decrease warfarin effectiveness?
alcohol, azathioprine, barbiturates, carbamazepine, cortisone, corticotropin, cyclophosphamide, dicloxacillin, haldol, phenytoin, prednisone, ranitidine, rifampin, spironolactone, sucralfate, trazodone, vitamin C
86
What are some common drugs that increase warfarin effectiveness?
alcohol, allopurinol, 5-ASA, amiodarone, ASA, Azole antifungals, cephalosporins, clarithro/erythro, 5-FU, flagyl, heparin, NSAIDs, neomycin, PPIs, penicillins, prednisone, propanolol, quinolones, ranitidine, thyroxine, TMP/SMX, tylenol, thrombolytics
87
How does heparin work?
- accelerates the reaction between thrombin and anti-thrombin III, accelerating the inhibition of thrombin (II) and other serine proteases (VII, IX, X, XI, and kallikreinin) by antithrombin III
- directly binds and inhibits coagulation proteases and is important for the selective inhibitor of thrombin, heparin cofactor II
- decreases platlelet aggregability
88
How does heparin affect PTT and INR?
- prolongs PTT by depleting intrinsic factors
| - prolongs INR
89
How long does it take to clear a dose of heparin?
6 hours
90
What are the complications of heparin?
- bleeding
- HIT I and HIT II (measure plt level q2d starting on day 4)
- alopecia
- osteoporosis
91
How does LMWH work?
inhibits activated factor X (Xa) but has less effect on antithrombin and on coagulation in general than the unfractionated heparin
92
How does ASA work?
- irreversibly blocks cyclooxygenase (prostaglandin synthesis), which catalyzes conversion of AA to endoperoxide compounds
- at appropriate doses it decreases the formation of prostaglandins and TXA2 but not the leukotrienes
93
How does ancrod work?
a thrombin-like enzyme produces anticoagulation by cleaving fibrinogen into fibrinopeptides that don't from stable microthrombi
94
What is the half life of ancord?
3-5 hours
95
How do medicinal leeches work?
- produce hirudin, a powerful and specific thrombin inhibitor
- action is independent of antithrombin III which means it can reach and inactivate fibrin-bound thrombin in thombi
- little effect on platelets or bleeding time
96
What are contraindications to thrombolytics?
- eye or CNS surgery within prev 2 weeks
- intracranial/spinal neoplasia or vascular anomalies
- stroke in prev 2 months
- active bleeding
- severe hypotension
- allergy to agent
97
What are the contradictions to thrombolytics in the setting of MI?
Absolute: active bleeding, aortic dissection, acute pericarditis, cerebral hemorrhage
Relative: GI or GU hemorrhage or stroke in last 6 months, major surgery or trauma in last 2-4 days, severe uncontrolled HTN, bleeding diasthesis or intracranial neoplasm, puncture of noncompressible vessel, significant chest trauma from CPR
