111 Disorders Of Hemostasis Flashcards
Vascular endothelium regulates? Formation.
Clot
What things does the vascular endothelium secrete to regulate clot formation – list 4
Tissue factor pathway inhibitor
Heparin sulfate.
Prostacyclin
Nature oxide.
CD 39
Bon Willebrand factor
What is the role of platelets?
One. Adhesion to sub endothelial connective tissue.
Two. Release of adenine diphosphate which amplifies aggregation
Three. Platelet aggregation over area of injury.
Four. Stabilization of haemostatic plug interaction with the coagulation system five. Stimulation of limiting reactions of platelet activity.
What is the intrinsic pathway of the coagulation cascade i.e.? What factors does it include?
12, 11, nine, eight
What lab value indicates the intrinsic pathway of the coagulation cascade?
APTT
What is the extrinsic pathway of the coagulation cascade and what lab value indicates this?
Seven and tissue factor
PT
What is included in the common pathway of the coagulation cascade?
Factor 10, prothrombin, which is two, thrombin, fibrinogen, which is one, firing clot, which is 13
Which three things in the coagulation cascade are required to turn the common pathway factor 10 into thrombin
Factor five
Calcium
Lipids
How did differentiate the Purpera associated with platelet disorders versus vasculitis?
Platelet: typically asymptomatic, not palpable.
Associated with vasculitis: burn/itch and is palpable
Name five features of coagulation disorders that differentiate from platelet disorders
One. Bleeding sources often intramuscular or deep soft tissue haematoma from small arterials.
Two congenital form of disease occurs predominantly in men
Three bleeding after surgery or trauma but maybe delayed in onset up to 72 hours
Four. Epistaxis, menorahaggia, G.I. sources of bleeding are rare, whereas haematuria and haemarthrosis are common and severe cases.
Five. Bleeding time is normal accepting patients with von Willebrand disease.
What do I need to include in my clinical evaluation of a bleeding patient for a history?
Nature of the bleeding.
Sites of bleeding.
Challenges to haemostasis from prior experience and current.
Medication’s
Associated diseases, such as urea, liver, disease, infection, malignant neoplasm.
Transfusion history.
Family history
What is my physical exam for the bleeding patient?
Vital signs
Skin
Mosa
Lymphadenopathy
Abdomen
Joints.
Other sites of blood loss, including pelvic, rectal, urinary tract, intramuscular, or deep soft tissue
What are the main mechanisms of platelet disorders or low platelets?
One. Decrease production.
Two. Increased destruction.
Three. Dysfunction.
Four. Sequestration.
In low platelet disorders, what kind of things can cause decreased production
Drugs.
Toxins
Infection.
Hereditary concerns.
Can also be splenic sequestration
In disorders with low platelets, what kind of increased destruction categories and diseases might be seen?
One. Immunologic – vascular disease, lymphoma, leukemia, drug related, infection, post, transfusion, immune thrombopenia.
Mechanical: DC, TTP, HELLP
Vasculitis
Dilutional
What kind of platelet disfunction does Bon Willebrand’s disease have?
Adhesion defects
What different categories of disease can cause elevated platelet
Primary
Reactive.
Iron deficiency.
Infection or inflammation
Trauma.
Non-hematologic malignant disease.
Rebound from alcohol, sot, toxic drug therapy, folate, or B12 deficiency
Name 4 collagen vascular disorders that are inherited
Ehlers danlos
Osteogenesis imperfecta
Pseudoxanthoma elasticum
Hemorrhagic telangeftasia
Name six different vascular disorders that are acquired
Scurvy
Simple or senile Purpera
Purpera secondary to steroid abuse.
Vascular damage: infection, like meningitis, hemolytic, uremic syndrome, hypoxia
Name five different inherited coagulation disorders
Von Willebrand disease
Hemophilia/factor eight or haemophilia B/factor nine
Factor 13, factor 11, factor five, factor 10, factor seven or factor two
Afibroginemia or hypo
Name six different acquired coagulation disorders
Medication
Snakebite, venom induced consumptive coagulopathy
Liver disease,
DIC
Auto immune
Acquired factor inhibitors from treatment of congenital disease like haemophilia or malignancy
What are haemostasis tests you should order when concerned about a coagulopathy disorder
CBC and smear
Platelet count particular
Bleeding time.
PT
PTT
Friden factor levels and inhibited screens possible
As needed: electrolyte levels, glucose, BUN, creatinine and type in cross match
What does an INR test?
Extrinsic and common pathways: factor one, two, five, seven, 10
Deficiencies in fibrinogen, Promod, five, seven, 10
If an INR is isolated elevation, which factor deficiency should be suspected
Seven
What does a PTT test?
Intrinsic and common pathways: one, two, five, eight, nine, 10, 11, 12
If PTT is isolated and elevation, consider what deficiencies
12,Prekallikrien, high molecular weight kinogen
Eight, nine, 11
When is an anti-factor 10 a essay useful
Monitoring, unfractionated, heparin and low molecular weight heparin or for drug quantification of direct factor 10 a inhibitors, including rivaroxaban, apixaban
What does a fibrinogen level indicate?
Balance between production and consumption
Three causes of a decreased fibrinogen level
Severe liver disease.
Low production.
Over consumption, such as a DIC
When is a thrombin time helpful?
Analyzes the conversion of soluble fibrinogen into insoluble fiber, and is helpful for abnormalities of fibrinogen and inhibitors, dabigatran
What platelet level should patients be given a platelet transfusion as they are at risk, spontaneous bleeding regardless of any other cause?
Less than 10
What platelet level should people be given platelets prior to central line insertion
Less than 20
Patients receiving a lumbar puncture, should have a platelet transfusion below what level of platelets
50
For patients receiving neurosurgery or ophthalmology intervention, below what platelets should they receive a donation of platelets?
100
Name six drugs that can cause low platelets
Heparin
Quinine
Quinidine
Digoxin
Cell phon amides
Fatau
ASA
GP 2B3A inhibitors
Cocaine
What is heparin induced thrombocytopenia?
Antibody against PF4/heparin complex that causes a greater than 50% drop in platelets after 5 to 10 days of heparin
How to treat heparin induced thrombopenia?
Stop heparin
Steroids.
Fondaparinux or argatroban
Avoid warfarin until platelets, recover due to risk of thrombosis and skin necrosis
What is idiopathic thrombocytopenia pathophysiology?
IGG anti-platelet antibody, diagnosis of exclusion
For adult patients, how to treat idiopathic thrombocytopenia? During a life-threatening bleed.
Methyl prednisone 15 mg per kilogram, IV 0.7 mg per kilogram, platelet transfusion, call haematology
Thrombotic thrombocytopenic Purpera: what is this?
Antibodies against a DAMTS 13 and can be triggered by meds, including, Plavix, quinine, cyclosporine
How to treat thrombotic thrombopenia Purpera
Plasma paresis and rituximab
Prednisone 1 mg per kilogram
Consult heme
Don’t give plt unless they’re going to immediately die
How is the shiva toxin of E. coli 0157: H7 similar to TTP?
Shiva toxin inactivation of DAMTS 13, like TTP, but get more renal symptoms
Treatment of HUS
Fluids, supportive.
Dialysis.
No antibiotics and no ant motility drugs.
No plasma free ASIS and kids
What does Bon Willebrand factor lead to deficiencies in?
Factor eight
Abnormal platelet adhesiveness.
Abnormal vascular endothelium
Villa brand disease: platelets, PT, factor, INR, APTT, von Willebrand factor findings
Normal platelets, prolonged bleeding time, decrease factor eight, INR normal, APTT increased, von Willebrand factor decreased
How to generally treat von Wilburn factor disease
DDAVP 0.3 µg per kilogram for milder moderate
Humate p
Factor eight concentrated 50 units per KG for severe bleeding, FFP, TXA
What is the severe form of primary immune thrombocytopenia?
Acquired auto immune that has no parent trigger or associated condition.
Severe is less than 20
In children idiopathic immune thrombocytopenia is usually seen with what kind of prodrome
Viral
What secondary infections/diseases can cause immune thrombocytopenia
SLE, RA
Leukemia/lymphoma.
Post infection ITP with HIV, HRC, EBV, rubella, Veriella
Drug induced
How to treat newly diagnosed adult patients with autoimmune thrombocytopenia
Supportive.
Less than 30 asymptomatic or minor containers bleeding consider corticosteroids decks 40 mg PO/IV times four days, admission if platelets are less than 20, platelets are less than 10 consider IV in addition to steroids
How to manage peds patients with ITP?
Even with minor bleeding, typically no meds even if platelets are less than 20
Considered admission if uncertain, diagnosis or lack of close follow up.
New diagnosis: consider prednisone IV Auntie D immunoglobulin, but likely to be discussed with haematology
What is the 4T scoring system for heparin induced thrombocytopenia?
0 to 2 points considering thrombocytopenia, timing of platelet count, thrombosis sequela, other causes of thrombus piña appear or otherwise.
Less than three points is low probability of hit, 4 to 5 intermediate, 6 to 8 high
If 4T score for HIT is intermediate or high what to do?
Stop heparin, order immuno acid.
Manage thrombotic complications if necessary - consider Fonda or DOAC
Post transfusion Purpera what is this and when to treat
Risk factors include middle-aged women in previous pregnancy who had a transfusion recently within a week, platelets fall to less than 10
Treated with IV 1 g per kilogram IV plus or minus steroids
What are the two most common thrombotic microangiopathy?
TTP
HUS
Terrible triad of TTP
MAHA (shistocytes, high LDH)
Thrombosis, piña
End organ damage
Presentation of TTP symptoms: FATCRN
Fever
Anemia with haemolytic and shistocytes
Thrombus piña
Cardiac ischemia.
Renal manifestations, either protein or heme in urine (rarely renal failure)
Neuro symptoms
Treatment of TTP
Plasma exchange
Glucocorticoids, prednisone versus methyl prednisone.
If waiting for plasma exchange can give FFP.
If a factory rituximab
Avoid platelets as you can potentially just make them more thrombotic
What tests will help you to determine whether it’s TTP or DIC
IN ttp: PT, fibrinogen, D dimer are all normal wallabies are increased in DIC
What is DIC?
Disseminated intravascular coagulation affects the common acquired coagulopathy reflecting dysregulation of coagulation, and fibrinolytic pathways: a disorder of throbbing i.e. to a with excess generation of thrombosis, which leads to activation of factors five, eight, 13, 11
Fibrinogen to make a clot
Stimulating fibrinolysis
Stimulating platelets
Labs in DIC:
Increased INR.
Decreased platelets.
Increased D dimer.
Decreased fibrinogen
Increased APTT
How to treat DIC?
Platelet goal greater than 50
FFP goal INR 2 to 3, APTT less than 1.5 times normal
Vitamin K 10 mg IV.
Cryoprecipitate 10 units as contains fibrin
If macro clotting give IB heparin free PET
DIC:
Support coag magic 5 to consider
Fibrinogen greater than 1.5 with cryoprecipitate
Platelets greater than 50 - ply
Hematocrit, greater than 21% - blood
APTT less than 1.5 times control i.e. FFP.
INR less than 2 to 3 related to factor seven
What does HUS present with?
Abdominal pain, emesis, diarrhea, usually perceive the development of HUS by 5 to 10 days
HUS triad
Haemolytic anemia
Thrombopenia,
A.k.a.
What are three acquired causes of HUS
Shiga toxin ecoli
HIV
Strep pneumonia
Patient who might be initially thought to have ITP might actually have what hereditary thrombocytopenia disorders?
Adhesion defects Bernard soulier syndrome
Aggregation defect: glanzmann thrombasthenia
What is haemophilia a?
Deficiency in factor eight, X linked recessive disorder which requires replacement theory P and can lead to increase risk of aloe antibodies or inhibitors
Management of haemophilia a: chronic
Plasma derived factor eight.
Emicuximab - recant immunoglobulin that is used for prophylactic treatment
Needs to see a haematologist have a factor eight activity level, blood type, anti-hemophilic factor antibody status. I need to know their last day of hospitalization.
List eight reasons for factor replacement and haemophilia
Suspected bleeding into a joint or muscle.
Any significant injury to the head, neck, mouth or eyes.
Any newer, unusual headache, particularly falling trauma.
Severe pain or swelling at any location
All wounds that require surgical closure or wound did he?
History of trauma.
Prior to any invasive procedure surgery
Suspicion of uncontrolled G.I. bleed, or any symptoms of hypovolemia
Acute fracture, dislocation, or sprain
Suspicion of uncontrolled heavy menstrual bleeding, leading to anaemia or symptoms of hypovolemia.
When can you give DDAVP and haemophilia a?
Mild hemophilia a without inhibitors that are bleeding, but that is not life or limb, threatening, which increases factor 8 3 to 6 times their baseline level
What factor eight level to give in haemophilia a
One unit per KG factor eight will increase circulating factor eight level by 2%
Therefore, if the factor level is known dose equals desired times 8×0.5×8 KG.
An emergency situation assume level is 0%
Therefore goals for minor bleeding or trauma should be 40 to 50% and 80 to 100% for serious or like threatening bleed
In the emergency department, what recombinant factor eight a dose should be given? As compared to those not currently on.Emicuxumab?
90 µg per kilogram IV
Also consider giving p complex concentrate at a dose of 75 to 100 units per KGIV
What is haemophiliaB?
Factor nine deficiency, ex linked, similar clinical findings, and Homophilia a
How to treat haemophilia B?
Recombinant factor nine preparation or plasma drives concentration and emergency situations. Do not give FFP do not give cryer precipitated as it does not contain nine.
In severe bleeding, give 100 to 140 units per KGIV, which should result in a factor level of 80 to 100%
If they have inhibitors, they need haematology in the hospital: administer at 90 µg per kilogram IV and if not on prophylactic med (emicizumab) get PCC at 75 to 100 units per KGIV
What is warfarin?
Vitamin K antagonist
What are common DOACS?
Rivaroxaban
Apixaban
Xa Inhib
Dabigatran type of med
Direct thrombin inhibitor
Medication for reversal heparin
Stop the drug
Protamine sulphate 50 mg over 10 minutes - 1 mg of protamine for every hundred units of heparin (fractionated)
0.5 to 1 mg for every 1 mg of low molecular weight heparin: 1 mg protamine for every 1 mg low molecular weight heparin less than eight hours, 0.5 mg pram for every 1 mg low molecular weight heparin greater than eight hours
Reversal of dabigatran
Idarucizumab 5g iv
If unavailable considered PCC at 50 units per KGIV or 4FPCC
Considered dialysis
Reversal apixaban or river
Adnexet alpha
Or octoplex at dose of 2000 units IV 25 to 50 units per KG
When is a MHP reasonable
replacem entire bl vol or 10 units within 24h
transfusion >4 prbc within 1 our w/ ongoing losses
ttransfusion 6 prbc within 1 bleeding episode with ecpectation for ongoing losses
shock index..
Major hemorhage management
address source
early resus: map 50-60
reverse anticoag
+/- txa
MHP - how many plt
1 pool = 4 donors
MHP at HSC:
first, second receiving of fluids
first - 4 rbc
second only ffp
MTP rosen’s goals
hbg >70
inr <1.5
fibrinogen >1
plt >80
Complications MTP
coag
thrombocytopenia
hypothermia acidosis
hypomag
high citrate
hypoca
Wafarin: when to give vitamin K and octaplex vs supratherapeutic INR
octaplex if major, life bleed or active bleed and INR >10 and on warfarin
INR >5 just v and no bleed
Heparin: UFH vs LMWH reveral dose of protamine sulfate
1mg of protamine q100 units of UFH
0m5-1mg LMWH
Dabigatran: dose of reversal?
idarucizuab 5g IV
aka praxbind
or octaplex 50u/kg IV or dialysis as 57% drug reasonable in 4h
DOACS - reversal?
andexanet alfa or 4F PCC
d-dimer in DIC levels
15000-20000
Clinical features of HIT
thrombocytopenia
bleeding
thrombosis
skin necrosis
gangrene
organ ischemia/infarction
HUS vs TTP - moreso ?
HUS -renal vs TTP - cardiac, less renal
MC bleeding disorder
vwf
vwf 2 major functions
stabilizes half life of factor 8
promotes plt adhesion at site if issue
Type 1 vWD:
quantitative defect mc
Type 2 vWD:
quali defect
2A, B, M, N
Type 3 vWD:
severe defect pretty much none
vWD: nonsp tx
control bleeding sx (wo = IUD)
iron suppl
txa
topical hemostasis
vWD: if ongoing bleed despite conservative management
DDAVP 0.3mcg/kg specifically helpful for type I
IIb - bad to give!! get humate
Hemophilia: what percent are new mutations?
25-30% new mutations
Hemophilia: severe vs mod vs mild
sev <1u/dl, spont bleed
1-5
> 5
Hemophilia: prophylaxis
severe disease - coag factor or emicuzumab
Hemophilia: treat with hem A life thr bleed
50u/kg of factor 8 –> 100%
Hemophilia: treat with hem B life thr bleed
100 units/kg –> ~100%
Acquired hem A - what
plausible in pt >60
inhib against F8 to bypass - med per heme
Emergency managemnt of bl disorder
tx first, investifate later
ask for card
heme on call
txa 25mg/kg PO q6h
50 x weight = IU
