Heme 3 Flashcards
primary epistaxis is what?
platelets
what is secondary hemostasis
soluble, inactive protein-clotting factor change soluble fibrinogen to fibrin strands
clot containment
wound healing
what does nitric oxide cause
vasodilation
disurption of hemostasis leads to what
Bleeding
Thromboembolic events
causes of thrombocytopenia
Hemodilution
Decreased platelet production/bone marrow
Increased sequestration
Increased platelet destruction
labs to get with thrombocytopenia
CBC: platelet count, diff
% reticulated platelets
conditions w/ physiologic hemodiluation
pregnancy
causes of decreased platelet production
Cytotoxic chemo (usually reversible)
Aplastic anemia
Invasive malignancy (leukemia, multiple myeloma, myelofibrosis)
Stem cell defects
Metabolic issues/affect maturation (B12, folate, ETOH)
what causes increased sequestration theombocytopenia
splenomegaly
adavnced liver dz
myeloproliferative disorders (CML, myelofibrosis or splenic CA)
what causes increased platelet destruction
Autoimmune TCP (primary/platelets or 2ndary (SLE) Inc’d polyclonal antibodies against platelet membrane glycoprotein receptors (GPIIb/IIIa)
patient presents with petechial hemorrhage, mucosal bleeding, organomegaly, LAD (low grade fever possibly)
immune thrombocytopenia purpura (ITP)
signs and symptoms when platelets <20,000
what conditions are associated w/ thrombocytopenia in adults
HIV Hep C SLE IBD autoimmune hemolytic anemia (evans syndrome)
tx for thrombocytopenia
Manage underlying conditions
Steroids (daily prednisone vs. high dose dexamethasone/pulsed q 1-2 weeks x 6-8 doses); IVIG
Pre-op: consider platelet transfusion; life threatening
if a person has HIT what else may they react to?
LMWH (but seen more w/ UFH)
for patients on heparin therapy how many develop antibodies to heaprin and platelet factor 4 complex?
25%
labs for heparin induced TCP (HIT)
heparin-PF4 antibody complex (sensitive , non-specific)
Tx for HIT
direct thrombin inhibitor - lepirudin (renal) or argatroban (hepatic)
Non-immune cause TCP
thrombotic thrombocytopenia purpura (TTP)
what is congenital TTP?
due to a higher circulating leves of high molecular wt VFR multimers= increased platelet adhesion
tx for TTP?
steroids
ASA
plasmapheresis
Non-immune platelet destruction
Causes: sepsis, malignancy, liver dz, PIH/eclampsia
DIC
tx for HELLP syndrome
delivery of fetus and placenta
Labs w/ DIC
CBC: schistocytes/smear, prolonged PT & PTT, low fibrinogen, increased fibrin-split products
Tx for DIC
platelets
cryopreceipitate
FFP
disrupt cascade effect
secondary causes of VW dz
2ndary myeloma, myeloproliferative dz, monoclonal gammopathies = abnormal clearance of the larger vWF proteins in pt w/out hx bleeding
what is the most common hemophilia
hemophilia A
S&S: childhood origin (crawl, walk) or spontaneous bleeding into joints, muscles, soft tissue, retroperitoneum, intracranial bleed, mucosa, urine
Mild trauma, any surgery
Hemophilia
what does the prothrombin 20210 mutations cause?
increased prothrombin levels
what does a protein S deficiency lead to
superficial thrombophlebitis, DVT, PE
Protein C deficiency leads to what?
superficial phelbitis, DVT
inc’d marrow RBC & platelet production, inc’d viscosity & risk thromboembolism
Labs: elevated Hct, RBC parameter
polycythemia vera
tx for P vera
reduce RBCs - phlebotomy, hydroxyurea & prevent platelet activation - ASA
hypercoag state d/t platelets > 900,000/mcL
thrombocytosis
tx for thrombocytosis
hydroxyurea & bone marrow biopsy
Excessive RBC sensitivity to complement = inc’d clotting (intra-abdominal, cerebral), hemolysis, bone marrow aplasia
Smoky color urine (excess Hb)
Paroxysmal nocturnal hemoglobinuria
what test do you do for paroxysmal nocturnal hemoglobinuria
Ham’s test- RBC sensitivity to complement
how does smoking cause a prothrombotic state?
Endothelial damage platelet adhesion, reduced tPA production & TFPI = prothrombotic state
what is the most frequent test for HIT
HIPA- herparin-induced platelet aggregation assay
what is a platelet-activation test: patient’s serum is mixed w/donor platelets in presence of heparin; Positive test = aggregation of donor platelets = presence of antibodies to the heparin–PF4 complex
HIPA
tx for HIT
d/c heparin
may need direct thrombin inhibitor
tx for hyperhomocysteinemia
Rx: B12, B6 & folate supplementation
Binds heparin on EC to inactivate thrombin/common cascad
antithrombin III
(rare, genetic)
Arterial or venous clotting d/t excess circulating thrombin & reduced fibrinolytic activity
Dysfibrinogenemia
Vascular endothelial dysfunction, reduced NO, inc’d viscosity, inc’d vWF, inc’d fibrinogen = prothrombotic state & platelet activation
CHF
d/t infection, SLE/RA, CA, meds
Inc’d circulating TF & thrombin, dec’d fibrinolysis, reduced protein C activity
antiphospholipid syndrome
labs for antiphospholipid syndrome
high titers anti-hpospholipid antibodies
Endothelial dysfunction d/t renal failure, reduced NO production, inc’d circulating cytokines = hypercoag state
Uremia
tx for uremia
NO precursor L-arginine may help
how long should excessive clotting prophylaxis be given most surgery
Preventive therapy: 10 days post-op (up to 3 months/ortho)
how does estrogen effect clotting
Inc’d clotting factor levels, reduced effect protein S & antithrombin III
why are people w/ DM at a higher risk of clotting?
decreased insulin= NO production and increased platelet activation
increased insulin= blocked fibrinolytic pathway
what mutation Blocks anticoag effects of activated protein C to inactivate V
Leiden factor V mutation
why does cancer cause excessive clotting?
Tumor cells procoag effect = activation clotting cascade & inhibit fibrinolytic system
why does obesity/ elevated lipis cause excessive clotting
Lipoproteins can activate platelets & clotting pathway
VLDL: up regulates expression plasminogen activator inhibitor 1 gene & plasminogen activator inhibitor 1 antigen leads to platelet aggregation/clot formation
subclinical hyperthyroid causes increased what?
increased circulating clotting factor X
how does hypothyroid affect clotting?
inc’d fibrinogen, factor VII & plasminogen activator inhibitor, dec’d antithrombin III
how do thallassemia and sickel cell lead to excessive clotting
Inc’d platelet activation & thrombin
Dec’d NO & proteins C & S
why does sepsis put someone at risk for excessive clotting.
Inc’d tissue factor & activation extrinsic pathway
management of excessive clotting
reduce modifiable factors
alternative non-estrogen therapy
what are 2 anti-platelet drugs?
ASA
what are anti-thrombolytic drugs?
heparin and warfarin
irreversible inhibition COX-1 pathway
ASA
block platelet activation (blocks ADP receptor)
can combine w/ ASA
clopidogrel
increases platelet cyclic AMP = blocks activation
Best in combo w/ASA
Dipyridamole (Persantine)
inc antithrombin III & blocks intrinsic pathway; reverse w/protamine sulfate
Routine aPTT, heparin levels, platelet counts
if Low platelets – do HIT assay
Unfractionated heparin (UFH)
for HIT what do you give?
fondaparinux
danaproid
how can you reverse heparin
protamine sulfate
oral agent inhibits vitamin K dependent factors/extrinsic pathway; reversed w/Vit K, FFP
Monitor PT, INR
warfarin
contraindications w/ warfarin
frank bleeding, IUP, alcoholism, bleeding diathesis
Assess platelet function & body’s ability to form a clot
bleeding time
what is normal bleeding time?
1-9 minutes
Uses: detect a bleeding disorder, diagnose liver problems, screen people having surgery for unrecognized bleeding problems, monitor anticoagulant therapy
PT (prothrombin time)
Reflects activity most of the coagulation factors, including factor XII as well as “contact factors” (prekallikrein [PK] & high molecular weight kininogen [HMWK]) & factors XI, IX, and VIII in the intrinsic procoagulant pathway, as well as coagulation factors X, V, II & fibrinogen (factor I) in the common procoagulant pathway
aPTT (activated partial thromboplastin)
what is aPTT useful for?
monitor heparin therapy
screen for certain coagulation factor deficiencies
detect coagulation inhibitos (such as lupus anticoag), sepcific factor inhibitors and nonspecific inhibitors
what test evaluates the extrinsic and common pathways of the coagulation cascade
PT
what test evaluates the intrinsic and common pathway
PTT
Is PT is abnormal what should you consider
deficiencies II, V, VII, X
vitamin K dependent
if PT is prolonged and PTT is normal waht should you look at?
Liver disease
decreased vitamin K
decreased or defective factor VII
chronic low-grade DIC anticoagulation drug (warfarin) therapy
with normal PT and prolonged PTT what should you look at
decreased/ defective factor VIII, IX, or XI
VW disease
presence of lupus anticoag
is someon ehas prolonged PT and PTT what should you look at
decreased or defective factor I, II, V< or X
severe liver dz
acute DIC
basic labs for someone who is hypercoagable (CMP)
CMP: glucose, BUN, creatinine, lipid profile, TSH
what is a hypercoagulation panel
Protein S, protein C, antithrombin III, Leiden factor V mutation, prothrombin 20210A mutation, homocysteine level, antiphospholipid antibodies, fibrinogen level, anticardiolipin/antinuclear/lupus anticoagulant
what labs to look at if someone is on warfarin
Pt and INR
what labs to look at if someone is on heparin therapy
aPTT
what factor interact w/ Vit K synthesis
II, VII, IX & X & proteins C &S
