The following cases and commentary, which focus on hematology, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16). Part A of MKSAP 16 was released on July 31.
Case 1: Preoperative evaluation
A 32-year-old woman undergoes preoperative evaluation prior to a complex spinal surgery for repair of severe scoliosis. Her expected blood loss is 2.5 liters. She had a severe anaphylactic reaction during a prior erythrocyte transfusion she received for postpartum hemorrhage at age 25 years.
On physical examination, temperature is 36.8°C (98.4°F), blood pressure is 132/76 mm Hg, and pulse rate is 78/min.
Laboratory studies indicate a hemoglobin level of 13.6 g/dL (136 g/L), a leukocyte count of 7800/µL (7.8 × 109/L), and a platelet count of 186,000/µL (186 × 109/L). Previous laboratory studies indicate an IgG level of 868 mg/dL (8.68 g/L), an IgA level <5 mg/dL (0.05 g/L), and an IgM level of 64 mg/dL (0.64 g/L). No monoclonal spike is found on serum protein electrophoresis.
Which of the following is the most appropriate erythrocyte product for this patient?
A. Cytomegalovirus negative
D. Phenotypically matched
Case 2: Severe headache with history of myelodysplasia
A 48-year-old woman is evaluated in the emergency department for a severe headache that developed about 6 hours ago. She describes the headache as “the worst headache of her life,” and her family, who has accompanied her, notes she is now confused, and her speech is slurred. She has a history of myelodysplasia for which she has never required treatment, as well as poorly controlled hypertension. Medications are enalapril and amlodipine.
On physical examination, temperature is 36.4°C (97.6°F), blood pressure is 168/84 mm Hg, pulse rate is 66/min, and respiration rate is 18/min. The patient is confused. Her speech is slurred, and she has left-sided weakness. There is no lymphadenopathy or splenomegaly.
Laboratory studies show hemoglobin 10.3 g/dL (103 g/L), leukocyte count 4500/µL (4.5 × 109/L) with 63% neutrophils and 36% lymphocytes, mean corpuscular volume 106 fL and platelet count 32,000/µL (32 × 109/L). The prothrombin time, activated partial thromboplastin time, and liver chemistry values are normal.
A CT scan of the head shows an intracerebral bleed with extravasation of blood into the ventricular system.
Which of the following is the most appropriate minimum platelet threshold for this patient?
A. 30,000/µL (30 × 109/L)
B. 50,000/µL (50 × 109/L)
C. 100,000/µL (100 × 109/L)
D. 150,000/µL (150 × 109/L)
Case 3: Emergency transfusion for trauma patient
A 27-year-old man is admitted to the emergency department for injuries sustained in a motorcycle accident. There is no head trauma, but he has left lower-quadrant abdominal pain.
On physical examination, temperature is 36.8°C (98.4°F), blood pressure is 89/44 mm Hg, pulse rate is 112/min, and respiration rate is 14/min. Abdominal examination reveals left lower-quadrant tenderness, with rebound and guarding. The patient's mental status and neurologic examination findings are normal.
Laboratory studies show hemoglobin 8.7 g/dL (87 g/L), leukocyte count 11,600/µL (11.6 × 109/L), platelet count 188,000/µL (188 × 109/L), prothrombin time 12.1 s and activated partial thromboplastin time 35 s. The patient's blood type is A negative with no alloantibodies.
A CT scan of the abdomen confirms splenic laceration. The blood bank indicates that type A-negative blood is not available.
Which of the following is the most appropriate erythrocyte product for emergency transfusion in this patient?
A. A positive
B. AB negative
C. B positive
D. O negative
Case 4: Plasma exchange for myasthenia gravis
A 23-year-old woman is admitted to the hospital for plasma exchange. She was recently diagnosed with myasthenia gravis and remains symptomatic despite intravenous immune globulin and pyridostigmine. Medical history is otherwise noncontributory, and she has had no previous reaction to blood products.
Her respiratory function begins to worsen, and therapeutic plasma exchange is begun. Albumin is used as the replacement fluid, and citrate is used as the anticoagulant. One hour into the procedure, the patient becomes light-headed, vomits, develops extreme anxiety, and experiences perioral numbness and tingling.
On physical examination, temperature is 37.0°C (98.6°F), blood pressure is 121/48 mm Hg, pulse rate is 103/min, and respiration rate is 16/min. She has labored breathing, appears agitated, and has lid lag. She also has proximal muscle weakness and muscle twitching. Jugular venous distention and peripheral edema are absent.
Preplasmapheresis exchange laboratory studies show complete blood count normal, calcium 9.0 mg/dL (2.25 mmol/L), creatinine 0.8 mg/dL (70.7 µmol/L), magnesium 2.1 mg/dL (0.87 mmol/L), potassium 4.6 meq/L (4.6 mmol/L) and sodium 144 meq/L (144 mmol/L).
In addition to temporary cessation of plasma exchange, which of the following is the most appropriate treatment?
A. 0.9% Normal saline
B. Calcium gluconate
Case 5: Complications during transfusion
A 48-year-old woman is evaluated in the hospital for shortness of breath, chills, and fever that developed during transfusion of the first unit of packed erythrocytes she received following an uncomplicated left total hip arthroplasty.
On physical examination, temperature is 38.9°C (102.0°F), blood pressure is 116/68 mm Hg, pulse rate is 111/min, and respiration rate is 22/min. Oxygen saturation is 86% with the patient breathing oxygen, 2 liters/min by nasal cannula. There is no jugular venous distention or peripheral edema. Cardiopulmonary examination discloses tachycardia with a regular rhythm and no S3 or murmur.
Laboratory studies indicate a hemoglobin level of 9.3 g/dL (93 g/L), a leukocyte count of 9600/µL (9.6 × 109/L), and a platelet count of 198,000/µL (198 × 109/L).
A preoperative and postoperative type and screen indicate A-positive blood type with a negative antibody screen.
Diffuse bilateral infiltrates are seen on chest radiograph. An electrocardiogram shows sinus tachycardia but no ST changes.
Which of the following is the most likely diagnosis?
A. Acute hemolytic transfusion reaction
B. Febrile nonhemolytic transfusion reaction
C. Transfusion-associated circulatory overload
D. Transfusion-related acute lung injury
Case 6: Postpartum bleeding
A 22-year-old woman is evaluated in the hospital for severe vaginal bleeding that developed 24 hours after an uncomplicated, normal spontaneous vaginal delivery. The patient has no personal or family history of a bleeding disorder or menorrhagia. She underwent an uncomplicated tonsillectomy at age 5 years. Her only medication has been a prenatal vitamin.
On physical examination, temperature is normal, blood pressure is 89/55 mm Hg, pulse rate is 120/min, and respiration rate is 24/min. She has bleeding from venipuncture sites. Pelvic examination shows bleeding from the episiotomy suture and brisk cervical bleeding. Dilation and curettage, packing, and re-suturing are unsuccessful in stopping the bleeding.
Laboratory studies show hemoglobin 7.2 g/dL (72 g/L), leukocyte count 12,000 µL (12 × 109/L) with a normal differential, platelet count 350,000/µL (350 × 109/L), prothrombin time 11 s, activated partial thromboplastin time (aPTT) 75 s, aPTT mixing study 55 s (Normal range: 25-35 s), fibrinogen 345 mg/dL (3.5 g/L) and D-dimer 0.5 µg/mL (500 mg/L). The remaining laboratory studies are normal.
Which of the following is the most appropriate treatment?
C. Fresh frozen plasma
D. Recombinant activated factor VIIa
Answers and commentary
Correct answer: E. Washed.
Of the choices listed, the most appropriate erythrocyte product to minimize the risk of an anaphylactic transfusion reaction is washed erythrocytes. The diagnosis of severe IgA deficiency should be considered in any patient with a history of anaphylaxis during a blood transfusion. Most patients with IgA deficiency are asymptomatic although they are also prone to gastrointestinal infections (particularly Giardia lamblia) and have an increased risk for autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus. Some patients with severe IgA deficiency develop anti-IgA antibodies, which may lead to an anaphylactic reaction when blood products containing IgA are used in transfusion. Although fresh frozen plasma (FFP) is the main blood component containing anti-IgA antibodies, erythrocytes and platelet products also contain small amounts of plasma; consequently, anaphylaxis may occur with FFP, platelets, and erythrocytes. Washing erythrocytes and platelets can remove plasma proteins and greatly decrease the incidence of anaphylaxis. Transfusion of blood products from an IgA-deficient donor would be another viable option to minimize transfusion-associated risk of anaphylaxis.
Cytomegalovirus-negative blood would not be indicated in this patient who has normal T-cell function and is not at risk for cytomegalovirus infection.
γ-irradiation of erythrocytes minimizes the incidence of graft-versus-host disease by eradicating lymphocytes but would not decrease the risk for anaphylaxis and would not be indicated in this immunocompetent patient.
Leukoreduction of erythrocytes decreases the incidence of febrile nonhemolytic transfusion reactions, cytomegalovirus transmission, and alloimmunization but not anaphylaxis.
Phenotypically matched erythrocytes are indicated in patients in whom there is a high risk for alloimmunization and subsequent delayed hemolytic transfusion reaction such as those with sickle cell disease; however, phenotypically matched (matched for ABO, Rh, and Kell antigens) erythrocytes would not decrease the risk for anaphylaxis.
- Using washed erythrocytes and platelets minimizes the risk for transfusion-associated anaphylaxis.
Correct answer: C. 100,000/µL (100 × 109/L).
The most appropriate transfusion strategy is to maintain the platelet count at a level of 100,000/µL (100 × 109/L). This patient has life-threatening intracranial bleeding. The bleeding source is most likely due to hypertensive vasculopathy, and the patient is at risk for continued intracerebral bleeding because of her myelodysplasia-associated thrombocytopenia. Although no randomized trials exist, expert opinion and guidelines generally recommend maintaining the platelet count at a level greater than 100,000/µL (100 × 109/L) for the first few days after central nervous system bleeding or immediately prior to and after planned central nervous system surgery.
A platelet count of 30,000/µL (30 × 109/L) would not be high enough in this patient with intracranial bleeding.
A platelet count of 50,000/µL (50 × 109/L) is generally recommended for nonneurosurgical procedures or non-central nervous system bleeding, but transfusion to achieve a higher platelet count is recommended in this patient with intracranial hemorrhaging.
Guidelines do not suggest any additional benefit to maintaining a minimum platelet count greater than 100,000/µL (100 × 109/L).
- Platelet transfusion to maintain the platelet count at 100,000/µL (100 × 109/L) for the first few days after central nervous system bleeding or immediately prior to and after a planned central nervous system surgery is recommended.
Correct answer: D. O negative.
This patient should undergo transfusion with O-negative erythrocyte products. Whenever possible, erythrocytes should be ABO and Rh compatible between the recipient and the donor. When an exact ABO and Rh match is not available or when there is not time for blood typing and screening to be done for patients who require emergent transfusion, the least incompatible blood products should be transfused. Humans develop antibodies against ABO and Rh antigens not present on their erythrocytes. Therefore, this patient will have developed antibodies against blood group B but not blood group A. He will also have developed antibodies against Rh(D) because his blood type is Rh negative. Consequently, the most compatible blood of the choices listed is O negative. Because type O-negative blood lacks both A and B antigens as well as the Rh(D) antigen, it is considered the universal erythrocyte donor product and should be given when emergent transfusion is indicated and the recipient blood type is unknown or when an exact ABO and Rh match is not available.
The use of A-positive erythrocytes is not the best option because of Rh incompatibility, which could lead to an acute or delayed hemolytic transfusion reaction. However, this approach could be considered in emergency situations if A-negative and O-negative blood were not available.
AB-negative erythrocytes would be incompatible because of anti-B antibodies present in the patient's plasma, which would react against donor erythrocytes and could lead to an acute hemolytic transfusion reaction.
B-positive erythrocytes would also be both ABO and Rh incompatible and are therefore not an appropriate transfusion product for this patient.
- Type O-negative erythrocytes are considered the universal erythrocyte donor product and should be given when emergent transfusion is indicated and the recipient's blood type is unknown or when an exact ABO and Rh match is not available.
Correct answer: B. Calcium gluconate.
The most appropriate treatment is intravenous calcium gluconate. This patient's anxiety, vomiting, neurologic instability, and perioral numbness and tingling during plasma exchange are the classic symptoms of hypocalcemia, and, if left untreated, could lead to more severe neurologic and cardiac instability. Citrate, the anticoagulant used in most plasma exchange procedures, can lead to chelation of calcium and subsequent hypocalcemia. Given her symptoms, immediate infusion of intravenous calcium gluconate is warranted.
Intravenous fluids such as 0.9% normal saline would not correct this patient's hypocalcemia-related symptoms but would be helpful if there were associated hypotension.
Diphenhydramine, an antihistamine, would be useful if the patient had developed hives or other allergic symptoms but would not be indicated for her current symptoms.
Epinephrine would be indicated in the setting of anaphylaxis or more severe symptoms of cardiovascular instability but would not be the best option now because it will not reverse the patient's hypocalcemia.
Heparin would be warranted if a pulmonary embolism were suspected, but pulmonary embolism cannot explain her muscle twitching.
- Anxiety, vomiting, neurologic instability, and perioral numbness and tingling during plasma exchange are the classic symptoms of hypocalcemia, which requires immediate treatment with calcium gluconate.
Correct answer: D. Transfusion-related acute lung injury.
The most likely diagnosis is transfusion-related acute lung injury (TRALI). This patient developed a fever, dyspnea, diffuse pulmonary infiltrates, and hypoxia during a blood transfusion. This presentation is very consistent with TRALI, a reaction caused by antileukocyte antibodies in the donor blood product directed against recipient leukocytes, which then sequester in the lungs, usually during or within 6 hours of a transfusion. TRALI can occur with any blood product, even erythrocytes and platelets, which may have small amounts of plasma. Treatment of TRALI is primarily supportive, and most patients fully recover within days or 1 week.
An acute hemolytic transfusion reaction (AHTR) is most commonly caused by a clerical error leading to ABO incompatibility. Very early in the transfusion, affected patients develop hypotension and disseminated intravascular coagulation, but this patient presented primarily with hypoxia and is therefore unlikely to be experiencing an AHTR.
Febrile nonhemolytic transfusion reactions occur commonly during transfusion and are also characterized by fever. However, a febrile nonhemolytic transfusion reaction would not lead to hypoxia and pulmonary infiltrates.
TRALI can be difficult to distinguish from transfusion-associated circulatory overload. However, transfusion-associated circulatory overload is less likely than TRALI in this patient because she had only received a single unit of packed erythrocytes, had no underlying cardiac disease, and had no jugular venous distention, S3, or peripheral edema.
- Transfusion-related acute lung injury is characterized by hypoxia, and dyspnea, as well as fever and hypotension, occurring during or within hours of a transfusion and resembles noncardiac pulmonary edema.
Correct answer: D. Recombinant activated factor VIIa.
This patient requires recombinant activated factor VIIa (rVIIa). She had an uncomplicated vaginal delivery 24 hours ago and has no bleeding history and a prolonged activated partial thromboplastin time (aPTT) that failed to fully correct on 1:1 mixing with normal plasma. This suggests the presence of an acquired inhibitor, most likely to factor VIII, which can develop in the postpartum setting. rVIIa is approved for treating bleeding episodes in patients with acquired factor VIII inhibitors. rVIIa acts to bypass the need for factor VIII by binding to the surface of activated platelets, where it can generate factor Xa, leading to the production of a burst of thrombin and the formation of fibrin.
Disseminated intravascular coagulation (DIC) is characterized by a microangiopathic hemolytic anemia, low platelet levels, a prolonged prothrombin time, a low or decreasing fibrinogen level, and an elevated D-dimer level. This patient's normal prothrombin time, platelet count, and fibrinogen level make DIC less likely. Consequently, fresh frozen plasma and cryoprecipitate are not indicated.
Desmopressin is indicated in patients with von Willebrand disease (vWD), which can cause postpartum hemorrhage. However, this patient's lack of history of menorrhagia and absence of bleeding with tonsillectomy make vWD less likely; therefore, desmopressin is unlikely to be of benefit. Additionally, although desmopressin may be helpful in patients with acquired hemophilia who have low-titer inhibitor levels and mild mucocutaneous bleeding, it would be unlikely to provide significant benefit in patients with this degree of hemorrhage and aPTT prolongation.
- Recombinant activated factor VIIa is approved for treating bleeding episodes in patients with acquired factor VIII inhibitors.