Hematology

Question 1

Explain the adhesion part of platelets:

Answer 1

Following vessel injury, vWF binds to exposed collagen, and plts use the GP 1b to ADHERE to the damaged endothelium via vWF-GP Ib interaction.

Question 2

Explain the activation process:

Answer 2

Plt adhesion results in ACTIVATION, where GIIb/IIIa receptors are exposed and release of granules occur. Granules release thromboxane A2 and platelet activating factor which lead to aggregation and vasoconstriction.

Question 3

Final step of platelet formation:

Answer 3

The final step of the platelet plug involves the formation of thrombin by soluble coagulation factors and the plts AGGREGATE with each other by binding a crosslink, glue-like pattern of fibrinogen with the GP IIb/IIIa receptors.

Question 4

Vitamin k dependent clotting factors:

Answer 4

Factors: 2, 7, 9, 10; Proteins C, S

Question 5

Intrinsic pathway:

Answer 5

12 → 11 → 9 → 8 →10 →5 → 2 → 1. Answer A is the intrinsic pathway, which was thought of as initiation of the clot within the intravascular space. Answer B is the extrinsic pathway, which means that the clot formation is initiated outside the intravascular space.

Question 6

Does intrinsic or extrinsic start first? And if so-how?

Answer 6

In nearly, if not always, all cases, the coagulation pathway is initiated by the extrinsic pathway; that is endothelial damage results in release of tissue factor (3). The intrinsic pathway amplifies this only after the extrinsic pathway has been initiated.

Question 7

What is plasminogen? Where is it made and where can it be found? When is it incorporated? What activates it? And what does it do once activated?

Answer 7

Plasminogen is an inactive protein made by the liver and is found in the plasma. With endothelial damage, a platelet plug and fibrin formation occurs, as discussed in the above few questions. During the normal crosslinking of fibrin, plasminogen is incorporated, like tiny little time bombs ready to degrade fibrin once activated. With endothelial damage, not only does vWF bind to exposed collagen and tissue factor (Factor 3) released from the endothelial cells, but tPA is also released. tPA activates the plasminogen into plasmin which degrades cross-linked fibrin, releasing D-dimers (ignites the bombs). Plasmin activation COUNTERACTS the clotting cascade keeping it in check

Question 8

What inhibits actions of plasmin? What encourages it? (Drug wise)

Answer 8

But plasmin and tPA - you need to know and understand. Why? Aminocaproic acid (Amicar), Tranexamic acid, and Aprotinin inhibit the actions of plasmin and tPA promotes the action/ formation of plasmin.

Question 9

PT tests the _____ pathway?
PTT?
ACT
Bleeding time?

Answer 9

pT: Extrinsic
PTT: intrinsic
ACT: intrinsic
Bleeding time: platelet function

Question 10

Hemophilia A-deficiency in what? What percentage does a patient need to have for minor or major surgery?

Answer 10

Patients with haemophilia A have a factor 8 deficiency, which is a hereditary X- chromosome linked coagulopathy. Patients need 50% activity for minor surgery and 100% for major surgery.

Question 11

Hemophilia A treatment options: DDAVP, Cryo, factor 8, FFP?

Answer 11

Factor 8:c concentrate delivers 40 units per cc (meaning for an average patient with minimal activity they would only need 30-40 cc). Cryoprecipitate delivers 5-10 units per cc, making it the second best method. Typically a cryo bag will have about 100 units, leading to relatively large volumes needed. FFP has only 1 unit per cc, requiring at least 1.2 liters in a 70 kg patient to increase function to 50%. DDAVP works by up-regulating natural production of Factor 8 and von Willebrand (vWF), increasing present levels by 2-4 times. In this patient that would still be insufficient.

Question 12

Type 1 vWD: how does it work, what can you do to treat it? Is type 1 a quantitative or qualitative thing?

Answer 12

vWD is a common cause of hereditary coagulopathies and can lead to excessive surgical bleeding when in the homozygous form. There are many types of vWD, but by far the most common is Type I. Type I vWD has a quantitative defect in the vWF, but is responsive to DDAVP. DDAVP causes increased release of vWF from the endothelium, and is the preferred treatment for vWD in most instances.

Question 13

Tell me about type 2 and type 3 Von willebeand disease. What can you do to treat it?

Answer 13

Type IIB vWD, DDAVP can lead to paradoxical thrombosis and platelet consumption, and with Type III DDAVP is ineffective.

Question 14

I’m pts with VWF type 1, how can you treat it? Can you give Neuraxial, If so-what should you do?

Answer 14

For major surgery DDAVP alone is insufficient and Humate-P (factor 8/ vWF concentrate), cryoprecipitate, or FFP should be given. Far smaller volumes of cryoprecipitate and Humate-P are needed to raise factor 8 and vWF levels than FFP, and are therefore preferred treatments. vWD does not routinely rise PTT, but does increase bleeding time. There are no specific recommendations to withhold neuroaxial anesthetic techniques from patients with vWD (answer “Humate-P needs to be administered 30 minutes prior to epidural placement”), although many practitioners that would be willing to place an epidural or spinal in a patient with vWD would use DDAVP prior to epidural placement.

Question 15

DIC-how does it happen? What do the labs look like? Treatment? What causes increased D dimer? What are some causes?

Answer 15

DIC is a process of uncontrolled fibrin production with platelet and factor consumption. In the setting of sepsis, immune complexes, endotoxin, and cytokines cause the activation of various parts of the clotting cascade leading to wide-spread fibrin formation and thrombosis. Eventually as factors and platelets are consumed in forming the thromboses, there is a factor deficiency and thrombocytopaenia, leading to coagulopathy.

The process of widespread thrombosis also leads to increased fibrin breakdown by plasmin, leading to increased D-Dimers. Classically on labs one sees a low platelet count (must be present to fit definition of DIC), increased PT & PTT (consumption of factors), decreased fibrinogen and increased D-Dimers (fibrinolysis). Other common boards causes of DIC include retained placenta, fetal demise, burns, trauma, transfusion reactions, cancer, malignant hyperthermia, and embolism (especially amniotic). These result in increased tissue factor (TF) release and initiation of the extrinsic pathway.

Treatment: primary treatment is treating the underlying cause of DIC, but you can also give platelets, FFP, and cryo 😃

Question 16

IgG antibodies towards Plt antigens leads to Plt destruction and easy bleeding describes: __. How can the antibodies be removed? For major surgery, what should the platelets be? How much of an increase does one pack of platelets make?

Answer 16

ITP.
IgG antibodies can be removed by plasmapharesis or combated with IVIG therapy, steroids, and various immunosupressants
For major surgery, such as a splenectomy, the Plt count should be 100,000.
One unit of plasmapharesis Plts is the equivalent of a 6-pack. Therefore 6 X 5,000- 10,000 = 30,000 - 60,000 increase in Plt count

Question 17

ABO and Rh and their reactions with FFP and PRBC

Answer 17

This is a surprisingly misunderstood, but simple concept. Plasma from patients can contain anti-ABO and anti-Rh antibodies. Therefore a donor who is B, Rh – may have formed antibodies towards both the A antigen and the Rh antigen. Likewise, a patient who is AB, Rh + will not have antibodies against AB or Rh. Therefore, just as the O, Rh – patient is the universal pRBC donor, the AB, Rh+ patient is the universal FFP donor. That being said, even when wrong typed FFPs are given, it is rare to have a serious transfusion reaction.

Question 18

Cryo is a poor source of what?

Answer 18

Cryoprecipitate is a poor source of vitamin k dependent factors, including factor 9 which is responsible for Haemophilia B. Most common reasons to transfuse cryoprecipitate is low fibrinogen, vWF, or factor 8 (Haemophilia A).

Question 19

A patient presents with cerebral haemorrhage while on plavix and warfarin. What would you give?

Answer 19

Platelets for Plavix and recombinant factors 7 or 9 (PCC), which have 2,7,9,10 if 4 factor and no 7 if 3 factor

Question 20

When would you wash, irradiate, or leukoresuce blood cells?

Answer 20

Washing red blood cells (RBCs) is used, among other things, to remove IgA so that anaphylactic reactions don’t occur in IgA deficient patients. Leukocytes are responsible for febrile reactions and alloimmunization; therefore, the reduction of these cells reduces the risk of the complication. Irradiation, which destroys DNA, is used to prevent graft vs host disease. Recall that erythrocytes do not have DNA.

Question 21

What to do in a febrile hemolytic reaction-First____. Then:

Answer 21

For an acute haemolytic transfusion reaction, ABO incompatibility is the underlying cause in the great majority of cases. After the diagnosis is suspected, the transfusion should immediately be stopped. The next priority is maintaining cardiovascular stability with fluids and pressors if needed. The unused blood as well as a patient’s blood sample should be sent to the laboratory for Coombs test to confirm the diagnosis. One of the more common complications of acute haemolytic transfusion reactions is renal failure, partially due to haemoglobin obstructing the tubules. Therefore, the patient should be given copious amounts of fluids and diuretics (manitol, lasix). Bicarb administration can alkalinize the urine to hopefully prevent haemoglobin precipitation in the tubules.

Question 22

What will hemoglobin, bilirubin, and haptoglobin be in a febrile hemolytic reaction?

Answer 22

bilirubin (high), haemoglobin (low), and haptoglobin (low) will help confirm the diagnosis.

Question 23

Fluid bolus vs bicarbonate in a febrile hemolytic rxn:

Answer 23

Alternatively it could have had give fluid bolus and give bicarb as answer choices. Now what would you have done? Guess it depends on the vitals right? Chances are they haven’t provided you any. Now what?

Now you have entered the world of two right answers with one being better than the other. Trust you’re gut. Which one has more evidence? Which one is more important? You know the answer.

Fluid bolus!

Question 24

Delayed hemolytic transfusion. Why? What labs would you see? How do you differentiate it from a hematoma? Where does it take place?

Answer 24

These reactions occur typically to lesser antigens (Kidd, Kell, Duffy, etc) from an anamnestic response. The actual haemolysis occurs in the reticuloendothelial system, not intravascularly like ABO incompatibility. It appears a few days to a few weeks after the transfusion and can be differentiated from haematoma reabsorption by Coombs test.
Haptoglobin can also be normal with delayed hemolytic reactions.
Haptoglobin can also be normal with delayed hemolytic reactions.

Question 25

Febrile reactions with transfusions why? Do you stop transfusing? How do you treat?

Answer 25

Febrile reactions occur due to recipient antibodies towards donor WBCs, is often short lived, can be treated effectively with antipyretics, and is not a reason to stop the transfusion.

Question 26

What is post transfusion purpura?

Answer 26

Post-transfusion purpura is a very uncommon immunologic complication towards platelet surface proteins presenting with thrombocytopaenia a week after transfusion.

Question 27

What is Trali? What’s a two hit theory? What’s the theory of how it works? Onset when? Resolves when? Which type of increased bloood cells do you see?

Answer 27

Transfusion related acute lung injury (TRALI) is a significant transfusion related cause of morbidity and mortality. Its onset is typically within 2 hours, usually resolves within 48 hours, and causes a syndrome indistinguishable from ARDS/ ALI. The mechanism of TRALI and ARDS is very similar, that being capillary leak syndrome causing significant non-cardiogenic pulmonary oedema. The most popular theory for the mechanism of TRALI is transfused (donor) antibodies to HLA and other recipient antigens, although other theories exist. Also important in the theory of TRALI it requires two hits (two-hit theory of ARDS). The first hit causes sequestration of neutrophils to the lung (in this case the trauma). The second hit is the immune response as described above with activation of neutrophils and the entire immune response at the site of the lungs, explaining the well documented phenomenon of a transient leukopaenia.

Question 28

patient with TRALI is on the ventilator with airway pressure release ventilation (APRV) with high pressure of 34, low pressure of 0, inspiratory time of 4.6 seconds and a release time of 0.4 seconds with a FiO2 of 95%. Various modes including assist control and SIMV have also been tried. ABG (pH, PaO2, PaCO2): 7.22, 41, 52. What is the next best step in this patient’s management:

Answer 28

This patient has a significant shunt secondary to life threatening pulmonary oedema secondary to TRALI. Increasing the inspiratory pressure or time can improve oxygenation, but is unlikely to make a significant improvement in PaO2 as the inspiratory pressure is already dangerously high. An increase of 5% in FiO2 is unlikely to make a significant difference in most cases of low PaO2, much less one associated with such a significant VQ mismatch. Since TRALI is classically self-limited, ECMO would be a reasonable option. ECMO employs large canullae to deliver blood through a membrane oxygenator and deliver it back to the patient.

Venous-venous ECMO (v-v Ecmo) would be preferred to venous-arterial ECMO (v-a ECMO) as the heart is functioning well.

Question 29

TRALI is at a higher risk with which blood product?

Answer 29

FFP

Question 30

What is NPPE and why does it happen?

Answer 30

Negative pressure pulmonary oedema occurs with forceful inspiratory pressure against a closed glottis. This leads to negative intrathoracic pressures pulling water (by hydrostatic forces) from the interstitum into the alveolus. It is more common to occur in healthy adolescents and adults.

Question 31

What is TACO, and how does it differ from non cardiogenic pulmonary edema?

Answer 31

TACO presents with massive transfusion with other signs of cardiogenic pulmonary oedema. The problem here is fluid overload, not left ventricular dysfunction. Left ventricular end diastolic pressures (LVEDP) rise in response to the high volumes leading to increased hydrostatic forces in the interstitium causing fluid transudation into the alveoli. TRALI, ARDS, and pulmonary contusion are examples of non-cardiogenic pulmonary oedema, where LVEDP is normal or even reduced (classically).

Question 32

As a general rule of thumb, transfusing a pediatric patient 4 cc/ kg of pBRCs will raise the haemoglobin level by

Answer 32

1 g/dL

Question 33

Formula for ABL:

Answer 33

Estimated blood volume = Weight (Kg) X Blood volume per Kg

ABL* = Estimated blood volume X [(Starting Hb - Minimal allowable Hb)/Starting Hb)

Question 34

Blood value for preemie
BV neonate
Infant/toddler
Adult

Answer 34

100 preemie
85 full term neonate
75 infant/toddler
60-70 Adult

Question 35

Pt hemorrhages 2.5 L in 5 min. How different will his new Hgb be? Old one is 12. What will mixed venous saturation be?

Answer 35

Following massive haemorrhage, Hb is not expected to change as the concentration of RBCs in the blood that remains is the same as prior to the haemorrhage. Soon after the blood loss, extravascular water will be pulled into the intravascular space due to numerous mechanisms to restore intravascular volume. Mixed venous saturation; however, will fall precipitously as the amount of oxygen delivered to the tissues will be far lower than previously (due to less Hb mass and lower cardiac output

Question 36

Chances of HIV and Hep C from a blood transfusion? Hep B?

Answer 36

HIV and hep C: 1:2,000,000

Hep B 1:200,000

Question 37

PRBCs and hyperkalemia:

Answer 37

Potassium levels in pBRCs increase with shelf time, and massive transfusion can be associated with a mild hyperkalaemia that is easily handled by the kidneys in patients with adequate renal function

Question 38

Why does PRBC transfusion result ina metabolic alkalosis?

Answer 38

Citrate, when used a preservative, binds calcium during the transfusion and leads to intraoperative hypocalcaemia. Following large citrate loads, it is converted to bicarbonate in the liver leading to a metabolic alkalosis

Question 39

Can platelets be put through a warmer?

Answer 39

Technically yes, but no on boards.

Question 40

Which blood product is stored at RT and therefore is at a higher risk for causing infection?

Answer 40

Platelets are stored at room temperature for about 5 days. Because they are not stored at cooled temperatures, they have a higher theoretical and real risk of bacterial infections.

Question 41

What is a cause of HIT? Are platelets always low? What happens if you use warfarin during HIT? Can you ever give heparin again tonperson with HIT? What can you give to patients with this who have to have CABG?

Answer 41

HIT is due to antibodies towards heparin – platelet GP Ib complexes (and other sites) leading to thrombosis, platelet consumption, and of course thrombocytopaenia. HIT can be acute (low platelet count) or subacute (normal platelet count) and should be avoided in both cases
The use of warfarin during an active episode of HIT can cause limb gangrene. Recall that due to inhibition of protein C, warfarin causes a transient hypercoagulable state before being an effective anticoagulant. During this time, warfarin administration can worsen the thrombosis associated with HIT leading to limb ischaemia. Danaparoid is a safe alternative, as is lepirudin, fondaparunix, among others. Argatroban, as well as other medications, have served as heparin alternatives for coronary bypass surgery. After the episode of HIT has resolved and the patient no longer has measured anti-heparin antibodies, there is no strong evidence for an anamnestic response and heparin can be used again safely in this situation, although recommendations are to shorten the exposure as much as possible. As a side note, heparin and protamine were reviewed in questions 24 & 25 in the CTV section.

Question 42

If it ends with “ban”:

Answer 42

just remember if it ends with -ban its a direct factor Xa inhibitor

Question 43

Current transfusion recommendations:

Answer 43

Current recommendations for transfusions are < 10 g/ dl for patients with significant cardiac disease and ‘not less’ than 6 g/dl for everyone else.

Question 44

Will using colloid instead of crystalloid help prevent transfusion?

Answer 44

No

Question 45

Why are sickle cell patients anemic? Lack of what can cause aplastic crisis?

Answer 45

There are two keys to understand sickle cell: First, why are they anaemic and what needs to be done about that. Second, what promotes sickling and what crises can come about. Sickled cells are removed from the reticuloendothelial system after about a 10-20 day lifespan (compared to a normal of 120 days). This puts considerable strain and stress on the patient’s marrow to continue to produce red blood cells. Essential elemental deficiencies are common, including folate. The lack of folate (as well as infection with parvovirus interfering with erythropoeisis) can result in a life threatening aplastic anaemia (aplastic crisis), often requiring multiple transfusions. The reticuloendothelial system can be a cause of another crisis called the splenic sequestration crisis, where massive amounts of blood accumulate in the spleen (why – because that’s were they are being cleared!) leading to hypotension and even death. This is most common in infants and young children as spleen infarction (autosplenectomy) is essentially ubiquitous by the end of childhood.

Question 46

What increases sickling?

Answer 46

Therefore, conditions that increase sickling are hypoxia (decreased arterial saturation), acidosis or increased 2,3 DPG (right shift of Hb), hypotension, hypovolaemia, hyperviscosity, or vasoconstriction (decreased CO), and fever, shivering, or increased metabolic rate (increased VO2).

Question 47

Does sickle cell result in coronary issues?

Answer 47

It does not seem to result in coronary disease despite the very low oxygen tensions. Lung ischaemia presents with chest pain and is referred to as acute chest syndrome and can resemble acute coronary syndrome.

Question 48

Abdominal pain in sickle cell patients could be an abdominal pathology, or it could be-

Answer 48

Patients with sickle cell frequently have pigmented gallstones which often will require a cholecystectomy. In this case, the patient was stressing herself with tobacco and alcohol resulting in a vaso-occlusive crises where micro (and sometimes macro) infarcts occur resulting in pain, especially abdominal pain. Vaso-occlusive disease and thrombosis can occur systemically leading to strokes, osteomyelitis, aseptic necrosis of the femoral head, and renal failure, to name a few.

Question 49

Sickle cell patients transfusion goal: ____. Major complication of transfusion for sticklers

Answer 49

In the mid 1990s it was shown that simply transfusing sickle cell patients to a Hb level of 10 g/ dl is just as effective as transfusing until Hb SS levels are < 30% regarding various outcomes. In addition, by transfusing to a Hb of 10 g/dl, on average, fewer transfusions are needed as well as fewer transfusion related complications. Outside of the complications discussed earlier in this section regarding transfusions, haemochromatosis is a major problem for sicklers, from iron overload. Hydroxyurea is one of the few traditional medical treatments actually aimed at the underlying problem of sickle cell and not its secondary complications. Foetal Hb is not only unavailable for transfusion (hopefully for very obvious reasons), it theoretically provides no advantage over regular pRBC donation. There is no reason to suspect coronary disease in this patient, so a stress test is wasteful.

Question 50

Hyoo, iso, or hyper?
LR
NS
Plasmalyte
Why are plasmalyte and NaCl the choices of carriers for blood transfusions?
What about solutions with dextrose and 5% NS?
D5 1/4 NS?

Answer 50

LR is mildly hypotonic (but essentially iso), contains Na, Cl, K, Ca, and of course lactate, which is converted into bicarbonate in the liver. Normal saline is slightly hypertonic, containing only Na and Cl. Plasmalyte is isotonic with less chloride than NS or LR, also supplemented with K and Mg, but lacking Ca, making it and NS preferred carriers for blood transfusions (as citrate binds to calcium causing precipitation). Because of its high Cl concentration, NS can cause a non-gap metabolic acidosis (due to decreases in bicarbonate) of little clinical significance in most cases. Hypertonic solutions include isotonic solutions with added dextrose (such as D5LR) as well as 5% NS. D5 ¼ NS is isotonic.

Question 51

Colloids vs crystalloid-is one more effective? Quicker? Do surgical patients have more of an extra cellular or intracellular deficit?

Answer 51

Replacing intravascular volume with crystalloids takes 3-4 more times the volume than colloids (conventional teaching), and therefore colloid can replace intravascular volume quicker and last longer than crystalloids. As far as efficacy of restoring intravascular volume, crystalloids and colloids are equal so long as sufficient amounts are used. Surgical patients’ extracellular deficits most always exceed the intracellular deficit (answer C). In most surgical settings and among critically ill patients as a whole, colloids have not been able to demonstrate an advantage over crystalloids.