Coagulation Flashcards
How do you treat Hemophilia A?
Factor 8 deficiency
If severe, < 1% = Factor 8 concentrate @ home, factor 8 prior to surgery (12 hour half life in adults)
If mild, 6 - 30% = Microdeletion, underdiagnosed until adulthood - DDAVP 30 - 90m prior to surgery
How long do you give factor 8 to severe hemophilia a patients
days - weeks post surgery
what else can be used to treat hemophilia a
ffp, cryo, txa
15 - 20 mL/kg of FFP =
20 - 30% increase in any factor
how do you dx hemophilia a/b
prolonged aptt, gene, factor testing
anesthesia & hemophilia b
- hemoc consult
- replacement therapy (recombinant F9, purified F9, PCCs)
- continue replacement therapy for 18-24h
- txa
anesthesia & hemophilia a
- hemoc consult
- factor 8 at least > 50 % prior to surgery
- mild = ddvap 30m prior vs moderate = f8
- ffp/cryo/txa
hemophilia b mild vs severe
mild 5- 40%
severe < 1%
vwf antigen
antigenic determinant on VWF measured by immunoassay; usually low in type 1 & 2, absent in 3
ristocetin cofactor activity
functional assay of vwf activity based on plt aggregation with ristocetin. greatest decrease in type 2
type 1 vw dx
most common
mild - moderate reduction in level of VWF
mild symptoms - bruising, nosebleeds
type 1 vw dx labs
vwf-rco & vwf-ag < 30
factor 8 low or normal
type 2 vw
9 - 30 % of patients
qualitative defect of vwf
4 subtypes
type 2 vw labs
vwf-rco < 30
vwf-ag <30 - 200
factor 8 low or normal
type 3 vw dx
< 1 % of patients
nearly undetectable - severe quantitative phenotype
type 3 vw labs
vwf-rco & vwf-ag < 3
< 10 factor 8 (very low)
platelet pseudo type
defect in platelets g1b receptor, normal everything
type 1 tx
desmopressin
type 2 or type 3 tx
factor 8 concentrate, or platelets
replacement goals in vw dx - major dx
maintain factor 8 >/= 50 % for 1 week
prolonged tx in type 3 patients (> 1 week)
minor surgery & vw dx goals
factor 8 >/= 50% for 1 - 3 days pre and post > 20 - 30% for 4 - 7 days
dental extraction & vw dx goals
one infusion to achieve factor 8 > 50% or desmopressin for type 1
spontaneous bleeding
transfuse 20 - 40 units/kg
1 unit/kg of factor 8 =
2% increase
what is factor 8 called
antihemophilic factor
1/2 life 12 - 15h
source: FFP, FC, cryo
what is factor 9 called
christmas factor
1/2 life 18 - 30
source: FFP, PCC, FC
what causes DIC?
thrombin (which normally stays at the site of vascular injury), is generated in response to endotoxins, amniotic fluid embolism
leads to intravascular clotting which then disseminates
coagulation factors and platelets are used up
fibrinolysis is activated = bleeding
symptoms of DIC
chest pain. SOB, leg pain, can’t move
clotting/bleeding/both
hemorrhage IV sites, catheters, drains
name 9 causes of DIC
sepsis, surgery, or snake bites trauma or transfusion rx cancer burns frostbite pregnancy complications
tell me about tissue factor & DIC
TF is present in cell surfaces like endothelium, macrophages, monocytes and lung, brain, placenta
it is exposed, released, binds with F8 = 9 & 10 activation = thrombin = fibrin = boom, clot
what does fibrinolysis do
creates fibrin degredation products that
- inhibit plts aggregation
- have antithrombin activity
- impair fibrin polymerization
thrombin & DIC
have lots of thrombin generation leading to consumption of coags, leading to more bleeding
consumption of anticoag proteins indicued by thrombin can also lead to clots
blood tests in DIC
DIC panel
low platelets, low fibrinogen
high INR, PT, PTT, D-dimer (DVP)
DIC progression
non-overt = hypercoagulable overt = hypocoagulable
how to treat DIC
infection? abx
trauma? resuscitation
supportive: plt, cryo, fibrinogen, FFP, heparin, TCA, PCCs
procoagulant DIC tx
monitor tests
start LMWH
hyperfibrionlytic DIC tx
txa
blood products
what is thrombin
potent proinflammatory protein and platelet aggregator
neutralizing thrombin in DIC is crucial
how. to neutralize thrombin
thrombomodulin - limited by clinical tirals
direct thrombin inhibitors - no RCTs yet (ie dabigatrin bilavalirudin argatroban lepirudin)
blood products in dic
plt –> cryo or fibrinogen –> FFP
name the 6 aa in hgb beta chain
valine = histidine = leucine = thre = proline = glutamic acid
glutamic acid = sc dx
formation of hgb
- proerythroblast –> reticulocyte
- 2 succinyl-CoA (from kreb’s cycle) + 2 glycine –> pyrrole
- 4 pyrrole combine = protoporphyrin
- protoporphyrin + irone = heme
- heme + globin combine
- 4 subunit chains possible (alpha, beta, gamma, delta)
what is the most common hgb
hgb a = 2 alpha/2beta
genesis of rbc (7)
- pluripotent hematopoietic stem cell
- proerythroblast
erythroblast hgb synthesis starts - bosphil erythroblast
- polychromatophil erythroblast
- orthochromatic erythroblast
loses nucleus, organelles –> into blood - retic (3 days in marrow, 1 day in blood)
- erythrocyte
name 3 common d/o of hgb
- methemoglobin - altered affinity
- thalassemia - quantitative d/o of globin chain
- sickle cell - qualitative d/o of globin structure
cause of methemoglobinemia
iron in hgb is oxidized from ferrous (fe 2+) to ferric (fe 3+)
- congenital (globin chain mutation) or (methemoglobin reductase system mutation)
- acquired (toxic exposure that oxidizes hgb iron)
symptoms of methemoglobin
left shift in oxy/hgb curve
pt can tolerate up to 30%, < 1 % is normal
30 - 50% = muscle weakness, nausea, tachycardia
> 50 % = death
globin chain mutation in methhgb
mutations that stabilize heme iron in the ferric state, making it resistant to reduction by methemoglobin reductase system
asymptomatic b/c levels don’t exceed 30%
impaired reductase system
causes methemoglobinemia
mutations impair NADH and cytochrome b methemoglobin reductase resulting in methemoglobinemia < 25%
slate gray pseudocyanosis despite normal pao2
acquired methemoglobinemia
rare
infants have lower levels of reductase (nitrates in well water, or oragel)
topical anesthetics (benzocaine)
anesthesia & methemoglobinemia
- avoid hypoxia and acidosis
- supplemental oxygen won’t help
- pulse ox won’t work
- a-line. EKG. blood sample (chocolate)
- avoid LA, nitrates, nitric oxide
treatment of methemoglobinemia
oxygen
1-2 mg/kg methylene blue over 3-5 m
repeat q30m if needed
METHYLENE BLUE NEEDS G6PD B/C USES REDUCTASE SYSTEM
HOW does methylene blue work
acts as an electron donor for the nonenzymatic reduction of methemoglobin
nadph converts methylene blue - leukomethylene using nadph
b-thalassemia =
an inherited defect in globin chain synthesis
contributes to anemia by :
1. inadequate formation of hba = microcytic rbcs
2. excess unpaired a-globin chains form toxic stuff that damage baby erythroids
a-thalassemia
deletion of one or more a-globin genes
ineffective erythropoiesis and hemolysis less pronounced than b but ineffective oxygen tissue delivery remains
thalassemia major & 3 defects
life-threatening - tx for the first few years
3 defects that depress oxygen-carrying capacity
1. ineffective erythropoiesis
2. hemolytic anemia
3. hypochromia and microcytosis
s/s thalassemia major (4)
damaged rbcs
bone hyperplasia
splenomegaly
death d/t chf & arrhythmias
anesthesia & thalassemia
mild = chronic, compensated anemia (preop tx for a hgb 10)
severe = spleno/hepatomegaly, skeletal malformations, chf, iron overload, cirrhosis, rshf
infection - abx
dvt prophylaxis
difficult intubation
tell blood blank the thalassemia
pathophjys sickle cell
hgb s, genetic defect of hgb synthesis
precipitated hgb damages membranes = sickling crisis of ruptured cells = further decrease in oxygen tension = more sickling
severe anemia, painful episodes
transfusion goal scd
increase ratio of normal hgb to sickle hgb
anesthesia & scd
avoid 3h’s
- hypothermia
- hypoxia
- hypovolemia
anxiolytics
lots of narcs
t&c (hard if you had lots of txs)
tourniquet - c/i?
acute chest syndrome
pna on cxr 2-3 days postop hypoxemia, analgesia, blood tx nitric oxide? decrease if preop hct > 30%
where are rbcs made
bone marrow
stimulated by erythropoietin (glycoprotein formed in the kidneys)
what is anemia
reduced number of rbcs
hgb < 12 for girls, 13 for boys
3 causes of anemia
blood loss, decreased production, increased destruction
s/s anemia
yellow eyes pale, cold skin SOB weak changed stool color dizzy, fainting chest pain/angina/heart attack enlarged spleen
acute blood loss anemia
body replaces fluid part of plasma in 1-3 days leaving low concentration of rbcs
rbc normalizes in 3 - 6 weeks
chronic blood loss anemia
can’t absorb enough iron from gut to make hgb as rapidly as it is lost
rbcs are produced smaller, with smaller hgb inside microcytic anemic
transfusion trigger
10/30 rule (no evidence)
< 6 = evidence
ebl < 15 %
rarely need transfusion
ebl 30%
crystalloids/albumins
ebl 30 - 40%
rbc tx
ebl > 50%
massive tx
ffp and plt as well
ratio 1/1/1
name 4 types of anemia based on mechanism
- decreased production (iron, autoimmune)
- increased destruction (thalassemia, hemolytic anemia, SCD)
- blood loss
- infectious (malaria, babesia, parvo)
what causes iron deficiency anemia
nutritional
chronic gi bleeds/ menstraution
pregnancy
-mild anemia, 9 - 12-
iron deficiency anemia causes (2)
impaired rbc maturation and diminishes rbc production
microcytic hypochromic anemia
tx iron deficiency anemia
oral iron & postpone 2-4mo
IV iron & postpone 1-2w
RBC tx
hemolytic anemia labs (4)
increased retics
unconjugated hyperbilirubinemia
increased lactate dehydrogenase
decreased haptoglobin
scd affects what globin
b –> which leads to polymerization of sickle hgb (hb s) into long, stiff chains when its deoxygenated
scd tx
hydroxyurea which rasies hbF
stem cell transplants
autoimmune anemia tx
immunosupression & steroids
causes of autoimmune anemia (5)
igg/igm idiotpathic leukemia mono drug induced (pcn, quinidine)
hemolytic dx of newborn
fetus rhd antigen +
mother rhd antigen -
igg mediated
rh factor
rhesus factor - a protein found on the surface of rbcs
genetically inherited
factor refers to the rh (D) antigen only (there are several Rh antigens)
the rh (D) antigen is the most immunogenic of all the non-ABO antigens
g6pd deficiency & drugs to avoid
metoclopramide pcn & sulfa methylene blue hypothermia acidosis hyperglycemia infection
polycythemia s/s
hct > 55 - 60%
PCV
cyanosis, HA, dizzy, GI symptoms, hematemesis, melena hepatic/coronary/cerebral thrombosis leukemia engorged vessels bluish/ruddy skin marrow fibrosis
usually see in the 6th/7th decade
types of polycythemia
physiologic d/t low atmospheric oxygen polycythemia vera (hct @ 60 - 60%)
PCV treatment
phlebotomy
myelosuppressive drugs (hydroxyurea)
anticoags to decrease thrombosis risk
these ppl die within months from vascular complications if not treated
