Heme Flashcards
Mechanism of action of unfractionated heparin
Antithrombin III inhibits thrombin and factor Xa
5 contraindications to unfractionated heparin
Hypersensitivity Active GI bleed ICH Bacterial endocarditis HIT
Treatment of major bleeding on heparin
Stop heparin
Protamine 1 mg/100 units given over previous 4 hours, administer slowly as risk of anaphylaxis
What is HIT syndrome, diagnosis and treatment
Autoimmune response to heparin, presents as >50% reduction platelets or thrombosis. HIT assay confirms
Treat with direct thrombin inhibitor
Mechanism of action of LMWH
Inhibits factor Xa
Which patients require monitoring of factor Xa while on LMWH
GFR <50 (cleared by kidneys, needs dose adjustment)
Morbid obesity
Pregnancy
Fondaparinux: a) uses b) treatment of major bleeding c) mechanism
A) VTE, hip replacement prophylaxis
B) recombinant factor VIIa
C) inhibits factor X
Primary indication for direct thrombin inhibitors (lepirudin, bivalirudin)
Patients with HIT
No antidote exists, care is supportive
Which coagulation factors are inhibited by warfarin
II, VII, IX, X
90yo on warfarin for mechanical valve, INR is 10 with no active bleeding, how do you reverse
Hold warfarin
Vit k 2.5-5 mg po
Recheck INR
Warfarin reversal with any major bleeding
Hold warfarin
Vitamin K 10mg iv slow push (risk anaphylaxis)
FFP or PCC or recombinant factor VIIa
4 complications of warfarin
Under anticoagulation
Over anticoagulation (bleed)
Paradoxical thrombosis between 2nd and tenth day
Warfarin induced skin thrombosis
Reduce risk of last two by bridging with heparin
Mechanism of action of dabigatran, apixaban and Rivaroxaban
Dabi direct thrombin inhibitor
Rivaroxaban and apixaban factor Xa inhibitor
Management of major bleed on DOAC
Stop offending drug
Supportive management
PCC, FFP, antifibrinolytics eg tranexamic acid
What is bleeding due to with patients taking aspirin
Platelet dysfunction, not thrombocytopenia
Three classes of anti platelets and their mechanism of action
Aspirin: cox 1 inhibitor, prevents thromboxane A2 synthesis
Thienopyridines (clopidogrel): irreversibly inhibits platelet aggregation
Glycoprotein IIA/IIIb inhibitors (abciximab): inhibit platelet activation
What additives are in packed RBCs
Anticoagulant preservatives; citrate, phosphate, dextrose, adenine
How much volume is in one unit of adult and pediatric pRBCs
350 ml in adult
60 ml in peds
What should you do to reduce the risk of febrile nonhemolytic reactions and prevent sensitization in bone marrow eligible patients and reduce risk of CMV and HIV transmission in immunesuppressed
Use leukoreduced PRBCs
Indications for transfusion pRBCs
End organ damage related to anemia (ie MI, stroke)
Active or recent bleed with Hb level under 70, 80-100 in known cardiac disease
How much does one unit of pRBCs increase hemoglobin
10
Mechanism of action of tpa
Activates plasminogen to plasmin, breakdown of fibrinogen and cross linked fibrin
Define thrombocytopenia and name four causes
Platelets < 100
Decreased production, increased destruction, splenic sequestration
Transfusion threshold for platelets
Life threatening hemorrhage and abnormal platelets
Platelets under 10 (except ITP, TTP, HIT, HUS)
Bleeding under 50
Massive transfusion
Seven causes of increased platelet destruction
Immunologic: ITP HIT infection Leukaemia, lymphoma Mechanical: TTP HUS DIC HELLP
Four causes of decreased platelet production
Marrow infiltration
Drugs
Toxins
Infections
Treatment of ITP
Treat for severe bleeding under 50, platelet under 10 without bleeding
Steroids, IVIG for unresponsive to steroids, recalcitrant may need splenectomy
Platelet transfusion only for life threatening hemorrhage
Avoid NSAIDS and physical activity for two months
9 causes of DIC
Infection (most common): GP and GN sepsis, meningiococcemia, Rocky Mountain spotted fever, typhoid fever
Trauma (burns, crush, head injury)
Shock
Pregnancy complications (abruption, amniotic fluid embolus)
Transfusion and drug reaction
Carcinoma (lymphoma, leukaemia, adenocarcinoma)
Liver disease
ARDS
envenomation
Surgical procedures
Heat stroke
Laboratory findings in DIC
Coagulation product consumption: prolonged PT and PTT, low platelet, low fibrinogen, increased thrombin time
Active clot formation: elevated dimer
Microangiopathic hemolytic anemia:
Treatment of DIC
Treat underlying cause
Replace consumed coagulation factors: FFP and Cryo
Platelet transfusion under 50 of bleeding, 10 if not
If thrombosis predominated give heparin
Purpura fulminans (protein c deficiency) treat with protein c concentrate (see in severe sepsis, bruising then necrotic centre)
Function of vWF and treatment of Von willebrand disease
Facilitates adherence or platelets to injured blood vessels
Stabilized factor VIII in plasma
Treatment:
DDAVP (stimulates release of vWF and factor VIII)
vWF concentrate in all cases serious bleeding
Cryo if no vWF available but carries risk infection
What should you consider in someone with bleeding disorder but normal platelet, PT, PTT?
Von willebrand disease
Which factors are deficient in hemophilia a and b
A= VIII B= IX
Clinical symptoms hemophilia
Easy bruising, hemarthrosis, hematuria, muscle hematoma
excessive bleeding after procedures, severe/delayed bleeding with minor trauma
Management of bleeding or trauma in hemophilia A
Factor VIII replacement by site (weight based and dependent on intrinsic factor activity)
DDAVP in mild to moderate bleeding in hemophilia a
Treatment of hemophilia B
Factor ix replacement weight based and site based
Use in extreme caution with presence of inhibitors (clotting factor mixing test) as can cause anaphylaxis so use PCC or factor VIIa in these cases
9 massive transfusion complications
Hypocalcemia
Hypothermia
Acidosis
Hyperkalemia
TACO
TRALI (supportive) – see most commonly w FFP and platelets
Fever transfusion reaction
Acute hemolytic transfusion reaction (ABO incompatibility)
Allergic
Delayed transfusion reaction (extravascular hemolysis from small amounts RBC antibodies)
Graft vs host disease (irradiate platelets in immunecompromised)
Infection
How much does one unit of platelets elevate platelet level by
30
Three situations where you want to avoid platelet transfusion
ITP, TTP, HIT
What is in fibrinogen, how is it administered
All clotting factors, fibrinogen
Given as 4-6 units (250 ml volume each)
Indicated in significant hemorrhage secondary to coagulopathy
Needs to be cross matched
What is in Cryo and when is it indicated
VIII, XIII, vWF, fibrinogen
Indicated in low fibrinogen state plus hemorrhage
Consider in hemophilia and vW
What is in PCC
II, VII, IX, X (vit k dependent)
Give in life threatening hemorrhage
Needs to be given with vit k as is transient
Lower volume and faster than FFP
Diagnostic findings in hereditary spherocytosis
Treatment
Hemolytic anemia (extravascular)
Negative Coombs
Positive osmotic fragility test
Spherocytes on smear
Folic acid supplementation, some need splenectomy
Precipitants of G6PD
Lab findings
Treatment
Infection, fava beans, drugs (eg post malarial treatment)
Hemolytic anemia, hemoglobinuria, hyperbilirubinemia, Heinz bodies on smear and bite cells
Supportive treatment
Difference between warm and Cold autoimmune hemolytic anemia
Warm is IgG antibodies against RBCs antigens. Binds at body temp. Associated w lymphoproliferative disorders
Cold is igm antibodies. Binds at cool temp, assoc w EBV, lymphoma, mycoplasma
Two examples of alloimmune hemolytic anemia
Transfusion reaction
Hemolytic disease of the newborn
6 causes of microangiopathic hemolytic anemia
DIC TTP HUS pregnancy (HELLP) Malignant hypertension Malignancies
Hallmarks of TTP-HUS spectrum
Microangiopathic hemolytic anemia
Thrombocytopenia
Plus minus renal and neuro involvement
Clinical picture HUS
Children, bloody diarrhea
Renal dysfunction, anemia, thrombocytopenia, microangiopathic anemic
Can see jaundice, fever, purpura
Pathophysiology of renal failure and neuro involvement in HUS-TTP
Fibrin deposition and platelet aggregation lead to intravascular hemolysis, microthrombi in renal and CNS vasculature
Work up of TTP HUS
CBC hapto ldh smear Coombs to rule out autoimmune D-dimer, fibrinogen for DIC, ptt inr Stool for shiga toxin producing bacteria (e coli, salmonella, shigella) Creatinine Urine r and m
Classic cause of TTP
Congenital or acquired deficiency in ADAMTS13 protein activity
Management HUS
Supportive care
Plasma exchange in severe
No antibiotics
Management of TTP
Plasma exchange
Four types of thalassemia
Alpha minor: usually mild, asymptomatic
Alpha maj: fetal hydrops and demise
Beta min: asymptonatic, hypochromic, microcytic anemia
Beta maj: severe anemia, splenomegaly, frontal bossing, transfusion dependent (splenectomy can reduce need for this)
Pathophysiology of sickle cell
Autosomal recessive disease, structure of b globin chain
One chain is carrier, both is disease
Deoxygenated RBCs take on sickle shape, leads to obstruction of RBCs in microcirculatoin and vaso-occlusive ischemic tissue injury
3 most common precipitants sickle cell
Hypoxia
Dehydration
Infection
Possible indications of exchange transfusion in sickle cell disease
Acute CNS event
Acute chest syndrome
Cardiopulmonary collapse
Priapism
Work up of possible sickle cell pain crisis
CBC, retics (hemolysis or aplastic crisis), smear, urine, chest X-ray, culture
Bugs implicated in acute chest syndrome in sickle cell
Staph strep chlamydia and mycoplasma
RSV
Treatment acute chest syndrome
Oxygen Iv hydration Antibiotics Analgesia Exchange transfusion if multiple lobe involvement, severe hypoxia, refractory to antibiotics
Age of splenic sequestration crisis in sickle cell
6 mo to 6 years
9 possible presentations and complications of sickle cell disease
Stroke Acute chest syndrome Acute pain crisis Osteomyelitis (staph aureus, salmonella) Osteonecrosis Cholelithiasis Priapism Ulceration Aplastic anemia
Definition of polycythemia
165 women, 185 men
Causes polycythemia
Treatment
Primary (myeloproliferative)
Secondary (increased epo eg lung disease, high altitude, expo secreting tumor)
Phlebotomy is treatment
Complications polycythemia
Both thrombosis from hyperviscosity and bleeding from platelet dysfunction
Hypervolemia syndrome
Pathophysiology of methemoglobinemia
Oxidizing agents cause ferrous iron to change to ferric iron which can’t bind O2
5 causes of methemoglobinemia
Nitrates Lidocaine Benzocaine Sulfa Dapsone Pyridium
Clinical presentation methemoglobinemia
MI, seizures, coma, death
Cyanosis
Anxiety, headache, tachycardia
Pulse ox 80-85 no response to oxygen with normal PaO2 on abg
Co-oximetry confirms
Mortality with levels over 40%, symptoms over 20%
Treat with methylene blue 1-2 mg /kg contraindicated in G6PD
Causes of neutrophilia
Infection or inflammation (esp w left shift or increase in immature neutrophils) Stress reaction (exercise, seizures, trauma, ketosis)
What is a leukemoid reaction
Nonleukemic leukocytosis> 50
See in sepsis, tb, Hodgkins, metastatic non hem cancers
Four types of leukaemia
CML: adult, least common, Philadelphia chromosome, typically asymptomatic. Increased polymorphonuclear neutrophils and myelocytes
Aml: most common adult acute, anemia, thrombocytopenia, variable leukocyte, blasts
CLL: lymphadenopathy, lymphocytosis, neutropenia, anemia, thrombocytopenia
ALL: peds, oancytopenia, blasts.
Pathophysiology of multiple myeloma
Single plasma cell clone and immunoglobin proliferation
Complications of multiple myeloma
Hypercalcemia, pathological fracture, hyperviscosity syndrome, spinal cord compression syndrome
What type of malignancy has the Reed-Sternberg cell or owl eye cells
Hodgkin lymphoma
Which type of non Hodgkin lymphoma tends to be curable
Aggressive (eg diffuse large B cell, anaplastic large cell, brukittm peripheral T cell, lymphoblastic)
