coagulopathy/blood products

	PT	PTT	BT
Hemophilia A
Factor 7 deficiency
Factor 5 deficiency
vWF deficiency
Aspirin
Thrombocytopenia
DIC

• what type of blood product is given for:
•  fibrinogen deficiency
• lacking multiple coagulation factors
• second line for vWF disease
• second line for hemophilia A
• Hgb <7

• If an invasive procedure: how high do you want platelet count
• what if it is a neuro surgery

• How do I avoid/reduce the risk of the following reactions:
• acute hemolytic rxn
• delayed hemolytic transfusion
• febrile non hemolytic rxn
• anaphylaxis
• TRALI - transfusion related acute lung injury
• circulatory overload
• septic rxn
• graft vs host disease

E2 Answers

E2 G6PD Deficiency

The two vignettes below describe the same disease process. Read both of them and then answer the following questions.

Clinical Vignette 1
A 23-year-old man of Iranian origin consults his primary care provider about a skin rash. He has an intensely pruritic rash over his buttocks and back that has appeared spontaneously. He is referred to a dermatologist, who diagnoses dermatitis herpetiformis and prescribes dapsone. Two days later he develops severe nausea and exhaustion, and complains of passing dark urine. His wife notices he has become jaundiced. He goes to the  ER, where investigations reveal anemia (Hb 7.5 g/dL) and abnormal biochemistry (elevated blood urea, deranged liver function, and unconjugated hyperbilirubinemia). An urgent hematology consult is obtained and a diagnosis of drug-induced hemolytic anemia made.

Clinical Vignette 2
An 18-year-old Greek man presents to the ER with severe nausea, vomiting, and diarrhea. His mother explains that he had been at a lunch party with friends and none of the other guests were ill. The patient had ingested a meal of rice, meat, and freshly cooked beans. He has not had any significant illnesses in the past. Examination reveals a markedly dehydrated young man who is clinically anemic and jaundiced. Investigations show a hemoglobin of 5.1 g/dL, elevated WBC count with a predominant neutrophilia, elevated blood urea and creatinine, and deranged liver function. No urine can be obtained. Intravenous fluids are commenced, followed by a transfusion of packed red cells; the patient becomes acutely dyspneic, however, and chest x-ray shows features of pulmonary edema. A nephrologist is consulted. Intravenous diuretic therapy is prescribed, a urinary catheter inserted, and 30 mL of urine obtained that, on testing, shows a high urobilinogen and protein content.


A peripheral smear was done and is show below for both of these patients. What abnormalities do you see if any? Which of the two images was taken during active disease?

There are two images. The top left corner shows a supravital stain with Heinz bodies, which are inclusions representing denatured hemoglobin. The peripheral smear in the main box shows bite cells. Active hemolysis would be found during active intravascular hemolysis.


What do you think caused their visit to the ER? Name a reason for each patient. Was it an environmental or genetic cause? What is the their condition? Name other inciting factors.

Exposure to Dapsone. Ingestion of fava beans.

Genetic and Environmental. G6PD is an x-linked recessive(medit-greeks/italians and African americans) d/o that is activated when an oxidizing substance is encountered.

Oxidant stresses that induces hemolysis:
-infection (most common)
-Drugs (primaquine, chloroquine, dapsone, sulfonamides, nitrofurantoin)
-Fava beans (esp in Mediterranean variant)

What is a benefit of this condition? What anemia has the same benefit as this condition?

Plasmodium falciparum. Sickle cell anemia.

What is the main pathogenesis of this disease process in 3 sentences or less?

Decreased synthesis of reduced form of nicotinamide adenine dinucleotide phosphate(NADPH) and glutathoine (GSH) in the pentose phosphate pathway.

-GSH normally neutralizes hydrogen peroxide, an oxidant product in RBC metabolism
-in G6PD deficiency, peroxide oxidizes Hb, which precipitates in the form of Heinz bodies.

What is the treatment?

Avoid exposure to known oxidants. Usually hemolysis is self-limiting, with spontaneous resolution in a week or so.

(Clinical Vignette Adapted from EPOCRATES)

E2

The two vignettes below describe the same disease process. Read both of them and then answer the following questions.

Clinical Vignette 1
A 23-year-old man of Iranian origin consults his primary care provider about a skin rash. He has an intensely pruritic rash over his buttocks and back that has appeared spontaneously. He is referred to a dermatologist, who diagnoses dermatitis herpetiformis and prescribes dapsone. Two days later he develops severe nausea and exhaustion, and complains of passing dark urine. His wife notices he has become jaundiced. He goes to the  ER, where investigations reveal anemia (Hb 7.5 g/dL) and abnormal biochemistry (elevated blood urea, deranged liver function, and unconjugated hyperbilirubinemia). An urgent hematology consult is obtained and a diagnosis of drug-induced hemolytic anemia made.

Clinical Vignette 2
An 18-year-old Greek man presents to the ER with severe nausea, vomiting, and diarrhea. His mother explains that he had been at a lunch party with friends and none of the other guests were ill. The patient had ingested a meal of rice, meat, and freshly cooked beans. He has not had any significant illnesses in the past. Examination reveals a markedly dehydrated young man who is clinically anemic and jaundiced. Investigations show a hemoglobin of 5.1 g/dL, elevated WBC count with a predominant neutrophilia, elevated blood urea and creatinine, and deranged liver function. No urine can be obtained. Intravenous fluids are commenced, followed by a transfusion of packed red cells; the patient becomes acutely dyspneic, however, and chest x-ray shows features of pulmonary edema. A nephrologist is consulted. Intravenous diuretic therapy is prescribed, a urinary catheter inserted, and 30 mL of urine obtained that, on testing, shows a high urobilinogen and protein content.

1. A peripheral smear was done and is show below for both of these patients. What abnormalities do you see if any? Which of the two images was taken during active disease?

2. What do you think caused their visit to the ER? Name a reason for each patient. Was it an environmental or genetic cause? What is the their condition? Name other inciting factors. 


3. What is a benefit of this condition? What anemia has the same benefit as this condition?

4. What is the main pathogenesis of this disease process in 3 sentences or less?

5. What is the treatment?

Ben T.
(Clinical Vignettes adapted from EPOCRATES)

D2 Answers

Images:

Sickle

Auto Infarction of the spleen

extramedullary hematopoesis of the skull

3 is the medulla

Aplastic Anemia

Parvo virus B19

D3 Sickle Cell Anemia

A 25 yo African American man is admitted to your service, who initially presented to the ER complaining of abdominal and bilateral lower extremity pain. He’s been admitted 6 times before for the same pain that has occured in the same locations. When you examine him, you note he is febrile to 101 F, respiratory rate of 25 breaths per minute, normal bp, and slight tachycardia of 100bpm. Lung examination revels bronchial breath sounds and egophony in the right lung base. His O2 sat on 2L/min nasal cannula is 92%. Besides the usual abdominal and leg pain, he is now complaining of chest pain, which is worse on inspiration. Although he is tender on palpation of his extremities, the remainder of his examination is normal.

Lab results revealed elevated white blood cell and reticulocyte counts, and a hemoglobin and hematocrit that are slightly lower than baseline.

These are seen on the peripheral smear:

Why do you think he was admitted 6 times prior to this hospitalization? Sickle Cell Disease
What do you think is the reason he needed to be admitted to the hospital? Acute Chest Syndrome

Name the abnormality in this image? What does it indicate?
D3 Sickle Cell Anemia

A 25 yo African American man is admitted to your service, who initially presented to the ER complaining of abdominal and bilateral lower extremity pain. He’s been admitted 6 times before for the same pain that has occured in the same locations. When you examine him, you note he is febrile to 101 F, respiratory rate of 25 breaths per minute, normal bp, and slight tachycardia of 100bpm. Lung examination revels bronchial breath sounds and egophony in the right lung base. His O2 sat on 2L/min nasal cannula is 92%. Besides the usual abdominal and leg pain, he is now complaining of chest pain, which is worse on inspiration. Although he is tender on palpation of his extremities, the remainder of his examination is normal.

Lab results revealed elevated white blood cell and reticulocyte counts, and a hemoglobin and hematocrit that are slightly lower than baseline.

These are seen on the peripheral smear:

Why do you think he was admitted 6 times prior to this hospitalization? Sickle Cell Disease
What do you think is the reason he needed to be admitted to the hospital? Acute Chest Syndrome

Name the abnormality in this image? What does it indicate?

Extramedullary hematopoesis in the skull

What three things promote sickling? Hypoxia, acidosis, dehydration, or variations in body temperature?

People with sickle cell trait do you exhibit the same severity of symptoms. Using the picture of a kidney below, determine the number/name of the site that is most susceptible to sickling for people with sickle cell trait. Tell me why? 3/Medulla of the Kidney due to

Renal papillary necrosis.

What prevents sickling at birth and for how long?

HbF for up to 6 months

Using the history of the patient, describe what is happening to the organ below and how patient must be protected after this process? (provide specific medical treatment and for what organisms) Autoinfarction of the spleen. Need to protect against encapsulated organisms such as Strep pneumo and H. influenza.

The patient starts to get better, but then after he was visited by his nephew, who likes the image below, he begin to get worse.





You notice  pallor, weakness, and lethargy secondary to something severe you notice on his daily labs. The image below is what comes up in your mind:

What is happening? Describe the image and how it relates to what is normal. How will you treat it?

The patient was exposed to Parvovirus B19 and is now experiencing aplastic anemia.
Extramedullary hematopoesis in the skull

What three things promote sickling? Hypoxia, acidosis, dehydration, or variations in body temperature?

People with sickle cell trait do you exhibit the same severity of symptoms. Using the picture of a kidney below, determine the number/name of the site that is most susceptible to sickling for people with sickle cell trait. Tell me why? 3/Medulla of the Kidney due to

Renal papillary necrosis.

What prevents sickling at birth and for how long?

HbF for up to 6 months

Using the history of the patient, describe what is happening to the organ below and how patient must be protected after this process? (provide specific medical treatment and for what organisms) Autoinfarction of the spleen. Need to protect against encapsulated organisms such as Strep pneumo and H. influenza.

The patient starts to get better, but then after he was visited by his nephew, who likes the image below, he begin to get worse.





You notice  pallor, weakness, and lethargy secondary to something severe you notice on his daily labs. The image below is what comes up in your mind:

What is happening? Describe the image and how it relates to what is normal. How will you treat it?

The patient was exposed to Parvovirus B19 and is now experiencing aplastic anemia.

(Clinical Vignette Adapted from CaseFiles Internal Medicine)

D3

A 25 yo African American man is admitted to your service, who initially presented to the ER complaining of abdominal and bilateral lower extremity pain. He’s been admitted 6 times before for the same pain that has occured in the same locations. When you examine him, you note he is febrile to 101 F, respiratory rate of 25 breaths per minute, normal bp, and slight tachycardia of 100bpm. Lung examination revels bronchial breath sounds and egophony in the right lung base. His O2 sat on 2L/min nasal cannula is 92%. Besides the usual abdominal and leg pain, he is now complaining of chest pain, which is worse on inspiration. Although he is tender on palpation of his extremities, the remainder of his examination is normal.

Lab results revealed elevated white blood cell and reticulocyte counts, and a hemoglobin and hematocrit that are slightly lower than baseline. 

These are seen on the peripheral smear:

1. Why do you think he was admitted 6 times prior to this hospitalization? 

2. What do you think is the reason he needed to be admitted to the hospital? 

3. Name the abnormality in this image? What does it indicate?

4. What four things promote sickling? 

5. People with sickle cell trait do you exhibit the same severity of symptoms. Using the picture of a kidney below, determine the number/name of the site that is most susceptible to sickling for people with sickle cell trait. Tell me why? 

6. What prevents sickling at birth and for how long?

7. Using the history of the patient, describe what has happened to the organ below and how patient must be protected after this process? (provide specific medical treatment and for what organisms) 

The patient starts to get better, but then after he was visited by his nephew, who likes the image below, he begin to get worse. 

You notice  pallor, weakness, and lethargy secondary to something severe you notice on his daily labs. The image below is what comes up in your mind:

8. What is happening? Describe the image and how it relates to what is normal. How will you treat it?

Ben T.
(Clinical Vignette Adapted from CaseFiles Internal Medicine)

C2 Answers

RBC Agglutination

S

C2 Hemolytic Anemia

A previously healthy 61-year-old woman with past medical history of aortic valve replacement had spontaneous eruption of a lacy, net-like erythema of her entire skin, which was especially pronounced on her arms and legs. The erythema of her lower arms disappeared within 2 minutes after immersion into a water bath at exactly 37°C. Her blood displayed the following after being placed in a petri dish:


Describe what you see and your leading diagnosis.

Clumping of the blood.

You noticed that one blood smear wasn’t analyzed. Luckily, you were there to make the first impression. Determine what is abnormal in the following slide and two situations in which you would this abnormality.

Agglutination of RBC’s

She experienced exertional dyspnea and dyspnea at rest. Recently she was diagnosed with EBV infection after noting a significant decrease in energy.  On physical exam you noticed scleral icterus and an enlarged spleen. She mentioned to you that she stopped taking warfarin cause she wasn’t feeling well and forgot it.


What systemic process is going on? Provide a reason for what incited this event. (more than one is possible)

Autoimmune hemolytic anemia

What specific immunoglobulin is associated with this process?

IgM

Results on electrocardiography, echocardiography, radiography, and skin biopsy were normal, as were the differential blood count and kidney function. There was no evidence of vasculitis or the antiphospholipid-antibody syndrome.

What type of anemia is occurring?

Normocytic Anemia



. Why is the patient taking warfarin? What coagulation factors does this medicine work on?

The patient is taking warfarin because she has a valve replacement. Warfarin works on Coag factors 2, 7, 9, 10 plus protein C and Protein S.

You also notice the following image below. What do you think could be happening concomitantly?

Macroangiopathic Anemia due to physical damage by the valves

(Clinical Vignette adapted from NEJM)

C2

A previously healthy 61-year-old woman with past medical history of aortic valve replacement had spontaneous eruption of a lacy, net-like erythema of her entire skin, which was especially pronounced on her arms and legs. The erythema of her lower arms disappeared within 2 minutes after immersion into a water bath at exactly 37°C. Her blood displayed the following after being placed in a petri dish:

1. Describe what you see and your leading diagnosis.


2. You noticed that two blood smear weren't analyzed. Luckily, you were there to make the first impression. Determine what is abnormal in the following slides and the situations in which you would find this abnormality. 

She experienced exertional dyspnea and dyspnea at rest. Recently she was diagnosed with EBV infection after noting a significant decrease in energy.  On physical exam you noticed scleral icterus and an enlarged spleen. She mentioned to you that she stopped taking warfarin cause she wasn’t feeling well and forgot it.


3. What systemic process is going on? Provide a reason for what incited this event. (more than one is possible)


4. What specific immunoglobulin is associated with this process?


Results on electrocardiography, echocardiography, radiography, and skin biopsy were normal, as were the differential blood count and kidney function. There was no evidence of vasculitis or the antiphospholipid-antibody syndrome.

5. What type of anemia (in regards to size) is occurring?

6. Why is the patient taking warfarin? What coagulation factors does this medicine work on?

7. You also notice the following image below. What do you think could be happening concomitantly? 

Ben T.
(Clinical Vignette adapted from NEJM)

B2 Answers

B2 Fe Deficiency

A 26-year-old malnourished woman presented with a 4-day history of mouth pain and a 3-month history of fatigue, general malaise, and palpitations. Physical examination revealed pallor of the conjunctiva and nail beds, as well as as the following photo:


Name this condition.

Koilonychia


Laboratory studies revealed a hemoglobin level of 30 g per liter, a platelet count of 45,000 per cubic millimeter, and a leukocyte count of 4100 per cubic millimeter. More lab studies were not done due to financial restrictions in the Brazilian clinic you were working at. Knowing that the local area had a high prevalence of hookworm infection, what lab studies would you pursue if you could order more?

Iron StudiesB2 Fe Deficiency

A 26-year-old malnourished woman presented with a 4-day history of mouth pain and a 3-month history of fatigue, general malaise, and palpitations. Physical examination revealed pallor of the conjunctiva and nail beds, as well as as the following photo:


Name this condition.

Koilonychia


Laboratory studies revealed a hemoglobin level of 30 g per liter, a platelet count of 45,000 per cubic millimeter, and a leukocyte count of 4100 per cubic millimeter. More lab studies were not done due to financial restrictions in the Brazilian clinic you were working at. Knowing that the local area had a high prevalence of hookworm infection, what lab studies would you pursue if you could order more?

Iron Studies

A peripheral blood smear shows the following (see above):


Describe what abnormalities you see, if any.

The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

What is your leading diagnosis? Two clinical features have already been mentioned. Name a third. Name 3 things that could cause it.

Iron deficiency anemia. PICA

What would you expect the following labs to show in your diagnosis?
Decreased MCV
Decreased serum iron, iron saturation
Decreased serum ferritin
Increased TIBC, RDW


Put the following Stages of the etiology of this patient’s disease.


Absent Iron Stores
Decreased serum ferritin
decreased serum iron
increased TIBC
decreased iron saturation
Normocytic normochromic anemia
microcytic hypochromic anemia


Intraoral examination revealed an abscess, which was drained. The patient underwent blood transfusion; the repeat hemoglobin level was 71 g per liter, and there was clinically significant improvement in her systemic symptoms.


In what form is Iron absorbed? Where is it mostly absorbed?

Iron is absobed in the ferrous form Fe 2+ in the duodenum.


Your patient starts to complain she has trouble swallowing solid objects, but is able to drink fluids. What new syndrome comes to mind and what other clinical features are a part of it?

Plummer-Vinson Syndrome: esophageal web, iron deficiency anemia, achlorhydria, glossitis, koilonychia

(Clinical Vignette Adapted from NEJM)

B2

A 26-year-old malnourished woman presented with a 4-day history of mouth pain and a 3-month history of fatigue, general malaise, and palpitations. Physical examination revealed pallor of the conjunctiva and nail beds, as well as as the following photo:

1. Name this condition.


Laboratory studies revealed a hemoglobin level of 30 g per liter, a platelet count of 45,000 per cubic millimeter, and a leukocyte count of 4100 per cubic millimeter. More lab studies were not done due to financial restrictions in the Brazilian clinic you were working at. Knowing that the local area had a high prevalence of hookworm infection, what lab studies would you pursue if you could order more? 

 A peripheral blood smear shows the following:

2. Describe what abnormalities you see, if any. 

3. What is your leading diagnosis? Two clinical features have already been mentioned. Name a third.  Name 3 things that could cause it.


4. What would you expect the following labs to show in your diagnosis? (increase, decrease, stay the same)
- MCV
- serum iron, iron saturation
- serum ferritin
- TIBC, RDW


5. Put the following Stages of the etiology of this patient’s disease in order.

Decreased serum iron
Absent Iron Stores
Normocytic normochromic anemia
Decreased serum ferritin
Increased TIBC
Microcytic hypochromic anemia
Decreased Iron saturation




Intraoral examination revealed an abscess, which was drained. The patient underwent blood transfusion; the repeat hemoglobin level was 71 g per liter, and there was clinically significant improvement in her systemic symptoms. 


6. In what form is Iron absorbed? Where is it mostly absorbed?


7. Your patient starts to complain she has trouble swallowing solid objects, but is able to drink fluids. What new syndrome comes to mind and what other clinical features are a part of it? 

Clue:

Ben T.
(Clinical Vignette Adapted from NEJM)

A2 Answers

A2: B12 Deficiency

A 62-year-old man with a several-week history of fatigue, loss of appetite, and feeling feverish presented at the hospital with severe pallor and signs of left and right ventricular failure. Neurologic examination disclosed poor short-term memory and decreased sense of vibration in the legs.

An electrocardiogram showed changes consistent with the presence of cardiac ischemia. The hemoglobin level was 3.7 g per deciliter, with a mean corpuscular volume of 108 μm3, a white-cell count of 3200 per cubic millimeter, and a platelet count of 57,000 per cubic millimeter.



You review this slide of his peripheral smear. Comment on it and what it could mean. What are the possible diagnoses? Name three. B12, folate, and nonmegaloblastic anemia.

Hypersegemented neutrophils, megalocytes, basophilic stippling (thalassemia, anemia of chronic disease, iron deficiency, and lead poisnoning= baste the tail)


You look through the chart and you note that the patient had a severe history of Crohn's disease. 10 years ago he had a portion of his colon resected.

After you discover the previous surgery, what type of nutritional deficit are you most concerned about? B12 Deficiency
What do you think is the most likely diagnosis? Megaloblastic Anemia
What type of diet puts patients most at risk for this disease? Why is that the case? Vegan Diet. No animal products.
What is significant for the amount of time since this patient’s colon resection? What part of the colon do you think was resected? It takes 6-9 years for B12 stores in our live to run out. Folate stores run out in a month. HIs terminal ileum was most likely resected due to his history of Crohn’s disease.

What two specific lab tests/values will be elevated in this patient? Serum homocysteine and methylmalonic acid


Which of the following will administration of folate correct in this patient: (select the most correct answer(s). More than one is possible)
-Correct both B12 and folate deficiency completely?
-Correct Folate deficiency
-Correct B12 deficiency
-Correct the hematologic aspect of B12 deficiency
-Correct the neurologic aspect of B12 deficiency
-Neither correct B12 or folate deficiency completely

Name at 5 reasons for B12 deficiency?

Pure vegan diet, malnutrition, decreased intrinsic factor, gastric acid, intestinal reabsorption, pregnancy/lactation

(D latum, pancreatic insufficiency)

What is the most common reason for B12 deficiecy?

Pernicious anemia

What is the most common cause of folate deficiency?

Decreased intake -malnutrition, infants/elsderly, chronic alcholhilcs, goat milk
Malabsorption-celiac disease, bacterial overgrowth
Drug inhibition- 5 flurorouracil, methotrexate, bactrim, phenytoin, ocp, alchohol
Increased utilization- pregnancy/lactation, dissmeinated malignancy, severe hemolytic anemia
What other lab test could you order to differentiate between folate versus B12 deficiency?

Methylmalonic acid

What 5 factors are required in Cobalamin absorption from the diet?

Intrinsic factor, salivary gland enzymes, r binder,pancreatic proteases, b 12

What medications for GERD can cause a B12 deficiency? PPI’s


What other cell types are associated with a B12 deficiency? A histologic image is provided below as a clue.



small intestine epithelial cells

The image below is taken from the patient above? What abnormalities do you notice and what is this condition called?

Subacute combined degeneration thoracic cervical cord. note the pale areas of demylination in the posterior columns and the lateral cortical spinal tracts

Name some positive physical exam findings for this condition? (Things that you definitely checked because you learned this condition so well during 2nd year)

Rhomberg
MMSE (dementia)
Ataxia
Vibratory sensation and joint sense


(Clinical Vignette adapted from CaseFiles Internal Medicine).