Hematology in special populations (3)

Question 1

What is the purpose of platelets?

Answer 1

When there is damage to a blood vessels platelets create a plug which forms into a clot to stop the bleeding

Question 2

What is thrombocytopenia defined as?

Answer 2

Platelet count < 100,000 cells/mm^3
or >50% reduction in platelets from baseline

Question 3

What does thrombocytopenia present with clinically? (2)

Answer 3

Bruising
Bleeding
(due to the inability to form a clot and stop the leaking of the damaged vessel)

Question 4

In general, we treat thrombocytopenia based on what?

Answer 4

The underlying condition that is causing the thrombocytopenia (which is why the mechanism behind the thrombocytopenia is important to identify)

Question 5

What are the 2 broad reasons why platelets may be low?

Answer 5

1. Increased platelet destruction (platelets are being made but are being destroyed)
2. Decreased platelet production (not enough platelets are being made)

Question 6

What can cause increased platelet destruction? (3)

Answer 6

1. Infection
2. Drug induced (DITP) - usually within 5-10 of starting new medication
3. Immune mediated (ITP) - immune reaction which causes platelet destruction

Question 7

What can cause decreased platelet production?

Answer 7

1. Usually due to bone marrow failure
2. Chronic alcohol use
3. Infection

Question 8

Thrombocytopenia treatment approaches/options (4)

Answer 8

(treatment is based on underlying mechanism/cause)

1. Corticosteroids (if there is an immune component)
2. Intravenous immunoglobulin (IVIG) (if immune component)
3. Stop offending medication (if drug induced)
4. Plasma exchange (if needed to clean out antibodies or drug, but then is also treated with additional drug)

Question 9

Heparin induced thrombocytopenia (HIT) presentation

Answer 9

This is a life threatening condition after heparin exposure

Presents with thrombocytopenia (reduction in platelets) AND new thrombosis (usually DVT or PE)

Question 10

How does HIT occur?

Answer 10

occurs 5-10 days after heparin exposure
(due IgG antibodies forming immune complexes)

Less likely to happen with LMWH than unfractionated heparin infusion

Dose and duration dependent (DDD)

Question 11

How is HIT classified? (4 factors)

Answer 11

4Ts classification:
1. Thrombocytopenia level
2. Timing of onset
3. Thrombosis (new vs progression of previous)
4. Other causes

Question 12

HIT treatment (3 options)

Answer 12

First line: direct thrombin inhibitors
-argatroban, bivalirudin, dabigatran

Warfarin
-not used much, only if platelets are high (>150,000) or if patients have renal impairment (can’t use direct thrombin inhibitors with renal impairment)

Xa inhibitors
-Fondaparinux, edoxaban, rivaroxaban and apixaban

Question 13

What is pancytopenia? How does it present?

Answer 13

Pancytopenia is when everything is low - RBCs, WBCs, and platelets

So, presents with BIA…
B = bruising and bleeding (due to low platelets)
I = infection (due to low WBCs)
A = anemia (due to low RBCs)

Question 14

What are causes of pancytopenia (3) Why is this important to know?

Answer 14

Usually bone marrow dysfunction related…
Bone marrow underproduction
-aplastic anemia, toxins, drugs, SLE, radiation
Bone marrow infiltration
-malignancy, nutritional deficiencies (vitamin b12, folate, copper)

Peripheral destruction of blood cells
-immunologically mediated - autoimmune (SLE)

Splenic Sequestration
-occurs in cirrhosis

It is important to know what the cause is because that determines how we treat it

Question 15

Why is anemia common in cancer patients?

Answer 15

Chemotherapy
-destroys stem cells
-decreases erythrocyte production
-decreases life span of RBCs

Radiation
-decreases RBC production

Tumors
-cause hemorrhage
-can replace bone marrow with malignant cells
-can release cytokines that decrease erythrocyte production

Question 16

EPO for cancer associated anemia considerations

Answer 16

exogenous erythropoietin (EPO) is an option to increase RBC production in cancer associated anemia

However, it should only be used if cancer is not curative and hemoglobin is < 10 and the patient is suffering

With cancer, bone marrow is suppressed, giving EPO keeps pushing bone marrow to produce RBCs, but it is already week - will not lead to positive outcomes = puts patients at risk of side effects of EPO without the benefit

So can be used as a palliative approach maintain a goal hemoglobin at the lowest concentration needed to avoid transfusions

Question 17

What is normocytic anemia usually caused by?

Answer 17

Cancer (disease or chemo induced)
or CKD

Question 18

How can we improve hemoglobin response in patients with normocytic anemia associated with cancer or CKD?

Answer 18

By providing iron
-we want to improve the hgb response and avoid transfusions

Question 19

What is aplastic anemia?

Answer 19

Occurs when there is direct damage to pluripotent hematopoietic stem cells before they can differentiate into committed stem cells
-results in decreased production of all blood cells (erythrocytes, neutrophils, and platelets)

Can happen at any age, can be mild or severe, gradual or rapid, is difficult to treat

Can be drug induced but this is very rare (The highest incidence occurs in ages 10-25 years old and >60 years old)

Question 20

Aplastic anemia diagnosis criteria

Answer 20

Diagnosed if at least TWO of the following are present
-Neutropenia - WBC ≤ 3500 cells/mm3
-Platelet count ≤ 55,000 cells/mm3
-Hgb ≤ 10 g/dL
-Reticulocyte count ≤ 30,000 cells/mm3

(everything is low, even reticulocytes, because the stem cells cannot even differentiate into those)

Question 21

How is aplastic anemia classified?

Answer 21

►Moderate: at least 2 of the following: neutrophils < 1500 cells/mm3, platelets < 50,000 cells/mm3, Hgb < 10 g/dL

►Severe: at least 2 of the following: neutrophils < 500 cells/mm3, platelets < 20,000 cells/mm3, reticulocyte < 1%

►Very severe: severe aplastic anemia with neutrophil count < 200 cells/mm3

Question 22

How is aplastic anemia treated?

Answer 22

Polyclonal IgG (ATG)
or calcineurin inhibitor (cyclosporine)

Many patients require combination therapy:
ATG + cyclosporine + prednisone + eltrombopag

Question 23

What are the 2 types of ATG and which one is preferred for aplastic anemia?

Answer 23

(polyclonal IgG antibody)
There are 2 types:
Atgam (horse derived) and Thymoglobulin (rabbit derived)

Atgam (horse derived) is preferred because it has a higher response rate and higher 3 year survival rate

Question 24

Atgam administration consideration

Answer 24

(this is the horse derived ATG)

A test dose is recommended because patients can experience serum sickness

And patients should be premedicated with acetaminophen, diphenhydramine, and glucocorticoids (to prevent serum sickness)

Question 25

Calcineurin inhibitor considerations for aplastic anemia

Answer 25

(Cyclosporine)

There are different formulations of cyclosporine - and they are NOT dose equivalent

This is preferred in elderly/frail patients (but many patients require combination therapy anyways)

Usually used for 6 months

Question 26

What is hemolytic anemia?

Answer 26

The premature destruction of RBCs
-normal lifespan of RBC is 120 days, this is much less in hemolytic anemia

Can be drug induced but this is rare
Usually immunologic related mechanism

Question 27

What lab findings does hemolytic anemia present with?

Answer 27

Decreased RBC
Increased reticulocytes (to compensate, bone marrow is forming new RBCs)

Abnormal liver labs - low haptoglobin, increased direct and indirect bilirubin

Increased lactate dehydrogenase (LDH)

Usually elevated MCV (increased size to compensate for RBC destruction)

Question 28

Hemolytic anemia treatment

Answer 28

Glucocorticoids (prednisone, methylprednisolone, hydrocortisone)
-because it is often immunologic related mechanism

Usually in combination with rituximab (or other immunosuppressants)

Question 29

Rituximab use considerations (2)

Answer 29

This is a CD20 inhibitor used in combination with steroids for hemolytic anemia

Can cause infusion related reactions:
-Premedicate with diphenhydramine and acetaminophen
-start infusion at slow rate (titrate rate slowly)

Test for hepatitis B prior to initiation
(therapy can cause reactivation of hep b)

Question 30

What is pernicious anemia?

Answer 30

This occurs when patients cannot absorb vitamin B-12
can be due to weakened stomach lining, autoimmune condition, or loss of intrinsic factor required for absorption

If it is untreated can result in heart and nerve damage

Question 31

Pernicious anemia treatment

Answer 31

Lifelong vitamin b12 therapy
(since this type of anemia is caused by inability to absorb b12)