Hematology Flashcards
What is meaning of
Type?
Screen?
Crossmatch?
Type-> to know type of blood (5min)
Screen-> to see if recipient has AB’s (already know the type of ptn blood)
Crossmatch-> if patient test (+) for screen test meaning have AB’s, then you crossmatch it to see what kind of AB’s, done in 3 phases and takes > 45min
- immediate phase: check ABO/Rh, M,N,P, and Lewis
- incubation phase: done if immediate phase is positive, done at 37 degree in albumin (simulating physiological state, because immediate phase done just room temp which AB’s could be not detected in cold temp). It’s also the phase to check Rh (takes 45 min)
- antiglobulin phase-> done only if previous phase is (+) for Abs, and this is to identify the specific AB’s and can find the compatible blood donor bag (takes 90min)
Indications for RBC transfusion
1) increased O2 demand
2) limited capacity for CO
3) L-shift O2 dissociation curve
4) impaired O2 uptake (e.g sepsis)
5) ongoing blood loss
PRBC facts
- CPDA
- average Hct 70%, has 50mL of plasma
- shelf life 35-42 days
- stores at 4C
- washed for patients with rxn to protein, irradiated for WBCs
(((1Unit -> increases Hg by 1g/dL and Hct by 3%)))
FFP indications
1) single factor deficiency
2) correction of multiple factors deficiency + micro vascular bleeding or PT/PTT >1.5
3) massive transfusion 1:1:1 ratio
4) reversa of warfarin
Indications for platelets
1) <100k in closed cavity bleeding like neurosurgery
2) <50k with ongoing bleeding
3) <50k in normal patient undergoing invasive procedure like epidural
4) <10k asymptotic, to prevent spontaneous intracranial hemorrhage risk
5) bleeding due to platelets dysfunction like uremia
Platelets facts
- Stored room temperature therefore only viable for 5 days otherwise risk of infection increases
- ABO compatibly not required, but it is for Rh (to avoid Rh+ sensitization for childbearing age)
(((1 unit increases plt 10k, and 30-50k with apheresis unit)))
Cryopreciptate indications
1) low fibrinogen state in micro vascular bleeding (<100 mg/dL)
2) ppx for hemophilia, vWD, congenital dysfibrongenemia
3) bleeding due to uremia unresponsive to DDAVP
Cryopreciptate facts
Contains 8, 13, vWD, and fibrinogen
ABO compatibility not required
The only 2 products needs absolutely ABO compatibility are
pRBC + FFP
Platelets needs Rh compatibility but not ABO
Cryo none
The heights risk of infectious agent transmission through transfusion is
Bacterial infection especially in platelets 1/3000, and if pRBC 1/30,000
Then HBV 1/300,000
“Bacterial contamination” is correct because bacteria are more commonly found in blood products (especially platelets) compared the risk of TRALI, anaphylaxis and Hep B.
Rates of non-infectious transfusion-related reactions:
- Immunomodulation = 1/1
- Febrile reaction = 1/200
- Minor allergic reaction = 1/200
- Delayed hemolytic transfusion reaction (HTR) = 1/2000
- TRALI = 1/5000
- Acute HTR = 1/20,000
- Anaphylaxis = 1/20,000
- Graft versus host disease (GVHD) = unknown
What’s the non-infectious repeated rxn that occur almost all the time
Immunomodulation 1/1 (100%) and that reflects patients are immunosuppreset host state once they received transfusion and increases risk of malignancy recurrence, infection, progression of HIV due to donor WBCs
Febrile and minor allergic rxn comes second 1/200
Causes of
Acute HTR Delayed HTR Anaphylaxis Minor allergic rxn Febrile rxn TRALI GVHD
AHTR -> ABO incompatibility (ptn Ab against donor RBC)-> intravascular hemolysis
DHTR -> Anamnestic response time prior exposure to Ag (transfusion or pregnancy)-> extravascular hemolysis
Anaphylaxis-> IgA deficient ptn reacting to donor IgA
Mild allergic rxn->rxn to donor proteins (always with FFP)
Febrile rxn-> ptn Ab against donor WBC
TRALI-> leukocytosis initiating insult? Usually requires preexisting inflammatory state
GVHD -> donor lymphocytes rejecting host in immunocompermised
Why it’s not recommended for 1st degree relative to donate blood?
Risk of GVHD (donor lymphocytes recognize recipe as foreign Ags) this how immunocomperant can get GVHD
If needed then irradiation required
Not likely to occur with Cryo or FFP
Leukoreduction decreases risk of
CMV
Febrile rxn
Immunomodulation
Irradiation of product decreases risk of
GVHD
Massive transfusion risk
- Hypothermia (4 units pRBC -> decreases 1C)
- Coagulopathy
- fibrinogen decreases after 1 unit
- factors depleted after 2 units
- platelets decreases after 2.5 units
(That why we give Cryo,FFP, platelets 1:1:1) - Acidosis (pRBC is acidic)
- Hyperkalemia (k is in plasma and 1u pRBC has 50 ml of plasma which has 30mEq/L)
- hypoCa
The shortest t1/2 of all clotting factors is
Factor 7
Because it’s synthesized in liver
Normal values of BT, PT, PTT,TT
BT: 2-9 min
PT: 10-12 seconds (intrinsic pathway factor 7)
PTT: 25-35 seconds (extrinsic pathway, most sensitive detecting factor 8,9 and thrombin)
TT: 10-15 seconds (measures ability of thrombin to concert fibrinogen to fibrin, prolonged in fibrinogen deficiency)
The most difficult factor deficiency to manage is
13
Causes significant bleeding and no available test (dose not alter PTT)
That’s why it’s considered to be transfused as last resort
ACT test which coagulation pathway
Intrinsic pathway similar to PTT but less sensitive than PTT
Normal values 90-120 seconds
If there is no response to ACT despite giving heparin, think
Antithrombin 3 deficiency and treated by giving FFP
What dose Anti-Xa activity assay monitor for
LMWH
Indirect Xa inhibitors
UH
TEG shape and associated abnormalities
- long R and shallow alpha angle:
- small MA:
- no MA:
- wide MA and prolonged MA+x:
- long R and shallow alpha angle: coagulation factor deficiency
- small MA: plt dysfunction
- no MA:fibrinolysis
- wide MA and prolonged MA+x: hypercoagulable state
R, k, and alpha -> assess amount and function of coagulation factors
MA-> assess clot strength
MA+x -> rate of fibrinolysis
ADP receptor antagonist is
Clopidogrel (xeralto)
Non competitive and irreversible
Given to prevent stent occlusion
Abciximab, tirofiban, and eptifibatide are
Glycoproteins 2b/3a receptor antagonists
They are reversible with t1/2 2.5 hours except abxciximab 12 hours to 24 hours
Given only IV by cardiologist
SE: thrombocytopenia
They can cause prolongation of ACT test
MoA of herbal and vitamins causing bleeding
They generally (-) platelets function
Garlic, ginger, ginkgo biloba, grape seed
Saw palmetto
Feverfew
Flaxseed oil
Vitamin E and ginseng
Why PCC is preferred than FFP to reverse warfarin in urgent cases
It takes a lot volume amount for FFP to effectively reverse warfarin, and usually PCC preferred for patients who do not tolerate FFP > 15mL/kg
PCC contains which factors? Dose?
1972 and factor 5 is alternative
15IU/kg when INR < 5
30 IU/kg if INT > 5
SE is thrombotic events
Anticoagulants of choice for patients with history of HIT
Direct thrombin inhibitors (Hirudin, lepirudin, argotroban, bivalieudin)
Problems:
1) can’t monitor
2) can’t reverse it
Bivalirudin is metabolized by plasma proteases and so makes it good option for RF or Liver dysfunction patients
Desmopressin dose and indications
VWD (except type 2b is contraindicated)
Hemophilia A
0.3 mcg/kg administration for 30 min (to avoid excessive release of NO which may cause hypotension)
Anti fibrinolysis are
Aminocaproic acid (EACA) and TXA
They preserve clots already forms, but it will not generate new clots
They both bind reversibly to plasminogen
TXA more potent because it also directly inhibits plasmin
Both excerpted mainly in urine
A 67-year-old patient with a history of MI and CHF with LVEF of 40% developed increasing dyspnea post radical prostatectomy in the post-anesthesia care unit. He started receiving 4 units of packed red blood cells and 4 units of fresh frozen plasma 10 hours ago. SpO2 is 98% on 4L of the nasal cannula. Chest radiograph reveals bilateral infiltrates. Which one of the following mechanisms is most likely causing these symptoms?
A. Hyperkalemia
B. Hepatitis
C. Bacterial sepsis
D. Transfusion-associated graft-versus-host disease
E. Transfusion-related circulatory overload (TRCO)
Differentiating TRCO from TRALI can be difficult. TRCO is seen especially in elderly patients, small children, and patients with compromised left ventricular function. Unlike TRALI, TRCO patients usually respond well to diuretics and oxygen supplementation. Diagnostic criteria for TRALI include hypoxia and bilateral pulmonary edema that occur within 6 hours of transfusion and in the absence of intravascular fluid overload or heart failure. In the stem presented it is clear that with CHF, the patient is most likely suffering from volume overload. TRALI is the second-best answer.
A 56-year-old man with end-stage liver disease is scheduled to undergo an esophagogastroduodenoscopy to evaluate esophageal varices. Which one of the following actions is most likely to be impaired in this patient? A. Production of coagulation factor VIII B. Production of coagulation factor IV C. Vitamin K absorption D. Production of coagulation factor IX E. Production of coagulation factor III
The liver is responsible for producing the majority of the coagulation factors except for factors VIII (antihemophilic factor), IV (calcium), and III (tissue thromboplastin). Hepatocytes also manufacture many of the regulators of the coagulation cascade including protein C, protein S, antithrombin III, and plasminogen activator inhibitor. Factor IX is one of the coagulation factors that is made in the liver.
Vitamin K is a cofactor in the carboxylation of factors II, VII, IX, and X, and proteins C and S. The carboxylation of these factors allows them to form complexes with calcium and primes them for activation and participation in the clotting cascade. Vitamin K absorption is not dependent on liver function; however, depleted vitamin K can also lead to a prolonged prothrombin time.
A patient with end-stage renal disease requires anticoagulation in the ICU. Which of the following direct thrombin inhibitors is most appropriate for patients with pre-existing renal or hepatic impairment? A. Hirudin B. Lepirudin C. Bivalirudin D. Argatroban
“Bivalirudin” is correct because it is largely cleared by proteolysis by plasma whereas “hirudin,” “lepirudin,” and “argatroban” rely on hepatic and/or renal mechanisms for metabolism/clearance.
A patient is undergoing hepatectomy and over time develops diffuse bleeding. A blood sample is sent for thromboelastography (TEG). A decreased maximum amplitude on thromboelastography most likely represents which of the following? A. Decreased clotting factor activity B. Decreased platelet activity C. Hypercoagulability D. Accelerated fibrinolysis
“Decreased platelet activity” is correct because the TEG scan maximum amplitude is proportional to the integrity of the initial platelet plug. “Decreased clotting factor activity” and “accelerated fibrinolysis” are incorrect because they refer to the alpha angle and the downslope of the thromboelastography (TEG) scan respectively. “Hypercoagulability” is wrong because it would exhibit a larger maximum amplitude.
A patient in the ICU requires anesthesia consultation for multiple medical problems. He is on a variety of medications, one of which includes desmopressin. Which of the following statements best characterizes the pharmacology of desmopressin?
A. It only has antagonist activity at V2 receptors and not V1 receptors
B. It may useful in SIADH
C. It causes release of Von Willebrand factor (vWF), F VII and tissue plasminogen activator (TPA)
D. It does not influence the prolonged bleeding time caused by NSAIDs
“It only has antagonist activity V2 receptors and not V1 receptors” is correct because DDAVP is only active at V2 receptors, not V1. It is indicated in DI not SIADH. It causes release of vWF, F VIII, and TPA,” not F VII and “it decreases the prolonged bleeding time caused by NSAIDs” therefore the other answer choices are incorrect.
refractory hypotension to transfusion, think?? and look at urine for …?
This is a hemolytic transfusion reaction. In the context of a blood transfusion, hemoglobinuria or hemolysis should be assumed to be a hemolytic transfusion reaction until proven otherwise. Thus B is the best answer. Although giving calcium is reasonable, the dark urine strongly suggest hemolysis. Under general anesthesia, the only signs may be hemoglobinuria and hypotension. If a hemolytic reaction is suspect, transfusion should be stopped immediately and the blood bank should be notified. The blood bank should check all paperwork to ensure that the correct blood component was transfused to the patient. The primary emphasis of therapy should be directed toward maintaining urinary output in excess of 75 mL/hour by generous administration of intravenous fluids and diuretics. One approach includes the administration of lactated Ringer’s solution to maintain the central venous pressure between 10 and 15 cm H2O while initially administering 12.5 to 50 g of mannitol.
composition of cryoprecipitate?
2 factors 8, 13,
vWD,
fibrinogen & fibronectin
Cryoprecipitate contains factor VIII:C (i.e., procoagulant activity), vWF (i.e., von Willebrand factor), fibrinogen, factor XIII, and fibronectin, which is a glycoprotein that may play a role in reticuloendothelial clearance of foreign particles and bacteria from the blood. Cryoprecipitate contains no prothrombin
A patient in the operating room requires extensive transfusion due to large scale blood loss. Which of the following would be least likely to cause transfusion-related lung injury (TRALI)? A. Fresh frozen plasma B. Packed red blood cells C. Platelets D. Whole blood
“Packed red blood cells” is correct because the inciting factors that cause TRALI are thought to exist in the plasma phase of blood. Packed RBCs have the least amount of plasma compared to “fresh frozen plasma,” “platelets,” and “whole blood.” As a result the latter answers are incorrect.
A 5-year-old patient overdoses on his mother's warfarin. The patient is lethargic and has bright red blood per rectum. Decision is made to transfuse plasma for a grossly elevated INR. What potential complication may be seen? A. Hypocalcemia B. Hypothermia C. Hypokalemia D. Hypoproteinemia
Hypocalcemia is a complication of fresh frozen plasma (FFP) administration due to citrate toxicity. Citrate is used to chelate calcium (and magnesium) and is used to prevent the clotting of stored products. The highest concentration of citrate in stored blood products is FFP and Platelets. Hypocalcemia due to citrate toxicity is usually not a complication of packed red blood cell (PRBC) administration. Hypothermia, liver disease and pediatric patients exacerbate hypocalcemia making option A the correct answer.
Signs and symptoms of hypocalcemia include hypotension, decreased pulse pressure, arrhythmias, increased left ventricular end-diastolic pressure and central venous pressure, mental status changes, tetany, and laryngospasm. Citrate intoxication is rare but may also present with Chvostek sign (facial spasms when tapping on the facial nerve) or Trousseau sign (carpopedal spasm with occlusion of the brachial artery). Treatment options include calcium replacement and are based on T-wave changes. Of note, transfusion of red blood cells may result in hyperkalemia from lysed red cells and therefore hypokalemia is incorrect (option C). Hypoproteinemia is not associated with the transfusion of FFP; however, hypothermia may be associated with transfusing FFP and PRBCs but these products are usually given via fluid warmers to prevent this (options B and D).
Caffeine and theophylline may produce mild platelet inhibition due to a mechanism similar to which of the following drugs? A. Ibuprofen B. Clopidogrel C. Dipyridamole D. Abciximab
Dipyridamole is correct because it inhibits phosphodiesterase and increases cyclic adenosine monophosphate (cAMP) which induces plt inhibition. Caffeine, aminophylline, and theophylline will also similarly produce mild, reversible platelet inhibition by this mechanism.
A patient presents for major surgery in which blood transfusion is likely. If their blood type is group B, Rh positive, then they may safely receive packed red cells from donors with which one of the following blood types? A. AB+ and O+ B. B- and AB+ C. B- and O+ D. O+ and A- E. A+ and AB-
Patients with B+ blood contain Anti-A antibodies in their serum (see table 55-2 in Miller’s Anesthesia). Therefore, the anti-A will cause hemolysis to RBC with surface A antigens (i.e. group A and AB blood). The O blood group has no surface antigens and therefore will not react to anti-A or anti-B antibodies. Therefore, patients with the group B+ blood group may safely receive blood from a donor with B+, B-, O+, or O- groups.
Rh(D) compatibility is only a concern in Rh-negative individuals. Sixty to 70% of Rh(D)-negative recipients are immunized (produce anti-D) if they are given blood transfusions with Rh(D)-positive blood. About 85% of individuals possess the D antigen and are classified as Rh(D) positive; the remaining 15%, who lack the D antigen, are classified as Rh(D) negative.
Requirement for autologous donation and contraindications?
1) Hb > 11
2) Hct > 33%
3) last donation > 72 hours preop
4) no more than 10.5mL/kg (once a week)
CI
1) infection
2) Aortic stenosis
3) Unstable angina
4) Active seizures
5) MI or CVA within past 6 months
6) significant cardiac or pulmonary disease
7) High grade LAD disease
8) cynotic heart disease
9) uncontrolled HTN
What physiological effects of Acute Normovolemic Hemodilution? Benefit? Selection criteria?
1) decreases PaO2 (compensates by high FiO2)
2) reduces viscosity -> decrease PVR -> increases CO (this also compensate for low PaO2)
It’s value in protection of plasma and platelets from acquired coagulopathy of extracorporeal bypass
Criteria
1) if likelihood of transfusion >10%
2) preop Hgb >12
3) no coronary, pulmonary, renal, or liver disease
4) no sever HTN
5) no infection
Blood should be returned to patient within 8hours
Cell saver (intraop sequestration/autotransfusion) benefit? Contraindications?
Reduces tots blood loss and use of allogeneric RBC
CI
1) infection
2) malignant cels, bowel, or amniotic fluid contamination
Estimated blood loss needed to see benefit is >800 mL.
Retuned blood can be ~Hct 40-60% with saline aliquots of 125-225 mL
SE is dilution all coagulopathy with large volumes due to lost clotting factors and most platelets by wash out along with unfiltered thrombin and microfibrillar collage or cellulose products
SEs of recombinant Hgb
Most significant is MI (due to intense arterial vasoconstriction from NO scavenged by infuses rHb)
- Nephrotoxicity
- Left shift of O2-d-curve (it has very high affinity to O2)
Calcineuric inhibitors are
Cyclosporine and tacrolimus
They inhibit lymphocyte signaling (decreases IL-2)
SE:
1) neurotoxicity
2) Nephro toxicity (cause renal vasoconstriction that can be reversed by nicardipine?)
Siri Linus is newer drug that dose not have neuro or Nephro toxicity
A 50-year-old patient in the operating room receives multiple blood products including blood, plasma, and platelets to treat extensive surgical bleeding. Bilateral pulmonary edema and hypoxia secondary to transfusion-related acute lung injury (TRALI) usually occur within what timeframe post-transfusion?
Diagnostic criteria for TRALI include hypoxia and bilateral pulmonary edema that occur within 6 hours of transfusion and in the absence of intravascular fluid overload or heart failure. The pathogenesis of TRALI appears to be activation of neutrophils on the pulmonary vascular endothelium as a result of donor leukocyte antibodies, particularly anti-HLA and antineutrophil antibodies.
A patient undergoing major thoracic surgery requires a transfusion of cryoprecipitate to treat diffuse bleeding from the field. Which of the following statements best characterizes cryoprecipitate transfusions?
A. It requires ABO compatibility
B. It can be used to treat hemophilia type B
C. It can be used to treat Von Willebrand disease (vWD)
D. It is stored at 4 degrees Celsius
Choice C is correct since cryoprecipitate has von willebrands factor and can thus be used as part of the treatment of these patients. “It is stored at 4°C” is incorrect because cryo is stored at much colder temps (-20°C) hence the name cryo. ABO compatibility not absolutely required. It cannot be used to treat hemophilia B since it has no appreciable factor nine.
A patient presents for major surgery in which blood transfusion is likely. If their blood type is group B, Rh positive, then they may safely receive packed red cells from donors with which one of the following blood types?
A. AB+ and O+ B. B- and AB+ C. B- and O+ D. O+ and A- E. A+ and AB-
Patients with B+ blood contain Anti-A antibodies in their serum (see table 55-2 in Miller’s Anesthesia). Therefore, the anti-A will cause hemolysis to RBC with surface A antigens (i.e. group A and AB blood). The O blood group has no surface antigens and therefore will not react to anti-A or anti-B antibodies. Therefore, patients with the group B+ blood group may safely receive blood from a donor with B+, B-, O+, or O- groups. Rh(D) compatibility is only a concern in Rh-negative individuals. Sixty to 70% of Rh(D)-negative recipients are immunized (produce anti-D) if they are given blood transfusions with Rh(D)-positive blood. About 85% of individuals possess the D antigen and are classified as Rh(D) positive; the remaining 15%, who lack the D antigen, are classified as Rh(D) negative.
Desmopressin is contraindicated to which vWD type
2b
Desmopressin is contraindicated in patients with type 2B because it increases abnormal vWF and may result in thrombocytopenia.
Type 1 vWD, the most common form of vWD, is an autosomal-dominant inherited disorder characterized by a reduced level of vWF.
Type 2A vWD, an autosomal-dominant inherited disorder, produces a qualitative defect of the protein with a selective loss of intermediate and large plasma multimers, the most functionally active proteins.
Type 2B vWD, an autosomal-dominant inherited disorder, is characterized by thrombocytopenia and loss of large vWF multimers.
Type 2M vWD is associated with decrease binding of vWF to platelet glycoprotein Ib. Type 3 vWD, an autosomal-recessive inherited disorder, is associated with very low or undetectable levels of plasma and platelet vWF antigen and ristocetin cofactor activity along with a markedly reduced level of factor VIII coagulant
Who’s at risk for citrate toxicity
Citrate intoxication is not caused by the citrate ion per se; it occurs because citrate binds calcium. The signs of citrate intoxication are those of hypocalcemia: hypotension, narrow pulse pressure, and increased intraventricular end-diastolic pressure and central venous pressure. However, citrate intoxication is very rare. Having hypothermia, liver disease, liver transplantation, or hyperventilation or being a pediatric patient increases the possibility of citrate intoxication. The appearance of severe hypocalcemia during liver transplantation is well documented. The combination of infusion of large amounts of citrate (i.e., through blood transfusions) and of reduced metabolism from absent or reduced liver blood flow (i.e., in the anhepatic phases of liver transplantation) leads to citrate intoxication.
Signs and symptoms of hypocalcemia depend on the rapidity and the degree of reduction in ionized calcium. Most of these signs and symptoms are evident in the cardiovascular and neuromuscular systems and include paresthesias, irritability, seizures, hypotension, and myocardial depression. ECG changes associated with hypocalcemia are marked by prolongation of the QT interval. In the postoperative period after parathyroid resection, hypocalcemia-induced laryngospasm can be life-threatening. The other choices listed would not present with the signs described, nor would they occur in the immediate time frame presented.
TRALI
The focus of this question is the diagnostic criteria for TRALI. TRALI is now the most important cause of morbidity and mortality resulting from blood transfusions. This condition is seen within 6 hours of transfusion of one of more units of blood products (option A). Significantly, one must be able to rule out other causes of acute lung injury such as sepsis or ARDS (option D). There must also be an absence of hemodynamic overload, which is represented by normal LA pressure (< 18 mmHg) (option C). Pulmonary hypertension, congenital or acquired, would make the diagnosis of TRALI unlikely and hence why option D is the answer to this question. There are 2 mechanisms that are thought to lead to development of TRALI:
Immune type: caused by anti-HLA antibodies 1,2 and/or less frequent to HNA (human neutrophil antigen)
Non-immune type: related to transfusion of biologically active compounds. No antibodies are detected
Clinically TRALI may present as dyspnea and evidence of respiratory failure. The mainstay of treatment is to support lung function similar to ALI/ARDS protocols. Severe cases may need endotracheal intubation and mechanical ventilation. Of note, the risk for TRALI is higher with transfusion of fresh frozen plasma and platelets than with red blood cells.
