CPR1 - Clinical {1.09, 1.11, 1.15-1.16,2.06,2.08-2.09,2.12-2.13}

What is hypoplasia?

Incomplete or arrested development of an organ, below normal number of cells

What is hyperplasia?

Higher than normal number of cells

What is dysplasia?

Abnormal growth noted microscopically, not malignant

What is aplasia?

Congenital absence of an organ

What cells mediate aplastic anemia?

T cell mediated

What is the presentation of aplastic anemia?

dyspnea on exertion, fatigue, infection, bleeding, bruising, CBC: Low HGB, WBC, PLT

What is the criteria for sever aplastic anemia (SAA)?

Neutrophils <500/cmm, platelets <20,000/cmm, Reticulocytes <0-0.5%

What is the etiology of sever aplastic anemia (SAA)?

Fanconi’s anemia

What is the treatment for congenital sever aplastic anemia (SAA)?

Bone marrow transplant

What is the initial treatment of idiopathic severe aplastic anemia (SAA)?

Combination of immunosuppressive agents and bone marrow growth factors

What are some chemical causes of bone marrow aplasias?

Insecticides, benzene, high dose chemotherapy, toluene (glue), wood preservative PCP, Herbs

What infections cause bone marrow hypoplasia?

HIV, EBV, CMV, influenza, bacterial/fungal infections

What infections cause bone marrow aplasia?

Hepatitis, Parvo - RBC aplasia

What is myelophthisic anemia?

Anemia (cytopenias) due to marrow infiltration

What is myelofibrosis?

Abnormal proliferation of fibrous tissue, or even new bone formation in marrow

What is the blood count pattern of multi-lineage cytopenias/pancytopenia?

Anemia, leukopenia, thrombocytopenia, suggests a primary bone marrow disorder

What is thalassemia?

Heritable, microcytic, hypochromatic anemia; genetic defects result in decreased or absent production of mRNA and globin chain synthesis

What is alpha thalassemia usually caused by?

Gene deletion

What is beta thalassemia usually caused by?

Gene mutation

What is the result of one deletions in alpha thalassemia?

Silent carrier, no clinical significance

What is the result of two deletions in alpha thalassemia?

Mild hypochromic, microcytic anemia, α thal trait

What is the result of three deletions in alpha thalassemia?

Hgb H (β4), variable severity, but less severe than beta thal major

What is the result of four deletions in alpha thalassemia?

Barts HgB (γ4), hydrops fetalis, in utero or early neonatal death

What is the MCV value of one deletion in alpha thalassemia?

Borderline low (78-80fL)

What is the MCV value of two deletions in alpha thalassemia (α thal trait/α thalassemia minor)?

70-75 fL

How does the human body respond to alpha thalassemia with three deletions?

Make hemoglobin with four beta subunits or four gamma subunits

What are the characteristics of Hgb H (β4)?

Vulnerable to oxidation, gradually precipitates to form Heinz-like bodies of denatured hemoglobin

What is Bart’s hydrops fetalis syndrome?

Four deletion alpha thalassemia, massive edema and ascites caused by accumulation of serous fluid in fetal tissues as the result of sever anemia

What is the result of beta thalassemias?

Overproduction of alpha globulin chains, which precipitate in the cells causing ineffective erythropoiesis

How is beta-thalassemia major treated?

Chronic transfusion therapy, chelation, splenectomy, HSC transplant, RBC maturation agent (Luspatercept)

What is the pathophysiology of sideroblastic anemia?

Defects involving incorporation of iron into the heme molecule despite availability of iron stores

What is the most likely diagnosis for patient 1?

Beta thalassemia trait

What is the most likely diagnosis for patient 2?

Beta thalassemia major

What is the most likely diagnosis for patient 3?

Hgb H disease

What is the most likely diagnosis for patient 4?

Sickle cell disease

When is the CBC test used?

WBC analysis, RBC analysis, platelet analysis

In an anemic patient in which bone marrow is not responding properly. The reticulocyte count will be:

Low

In an anemic patient with a ____ reticulocyte count may reflect accelerated blood cell destruction.

Higher than expected

In an anemic patient a _____ reticulocyte count reflects that bone marrow is responding to anemia.

Appropriate

What are some physical features of iron deficiency anemia?

Pallor of mucus membranes, spoon nails (koilonychia), angular cheilitis

What are some issues with laboratory evaluations in ACD?

Ferritin may be falsely high if patient has an active infection or active inflammation

What are some laboratory evaluations that should be tested when ACD is suspected?

C reactive protein or erythrocyte sedimentation rate (measure of inflammation), soluble transferrin receptor levels, hepcidin levels

A patient with:

• low serum iron

• Elevated transferrin

• Low iron saturation

• Low ferritin

• Elevated soluble transferrin receptors

What is the most likely diagnosis?

Iron deficiency

A patient with:

• low serum iron

• Reduced transferrin

• Low iron saturation

• High ferritin

• Normal soluble transferrin receptors

What is the most likely diagnosis?

Anemia of chronic disease

What is disseminated intravascular disease (DIC)?

An acquired syndrome characterized by systemic intravascular coagulation producing both thrombosis and hemorrhage

What is the pathophysiology of DIC?

Activation of blood coagulation, suppression of physiologic anticoagulation pathways, impaired fibrinolysis, cytokines

How does suppression of physiologic anticoagulant pathways induce DIC?

Reduced ATIII levels, reduced activity of protein C and S, Insufficient regulation by TFPI

How do cytokines induce DIC?

IL-6/IL-1 mediate coagulation activity, TNF mediates dysregulation of anticoagulant pathways and fibrinolysis, IL-10 may modulate activity of coagulation

What are some clinical manifestations of DIC?

Oozing blood from wound sites, petechiae, purpura and echymosis

How do you treat DIC?

Stop the triggering process, supportive therapy (Platelets, fresh frozen plasma, cryoprecipitate)

What is Bernard-Soulier syndrome?

Defective adhesion, deficiency in GPIb/IX receptor, autosomal recessive

What is Glanzmann thromboasthenia?

Defective aggregation, dysfunction in GPIIb/IIIa, autosomal recessive

What are storage pool disorders?

Defective release of mediators (ADP, Thromboxane)

What is immune thrombocytopenic purpura (ITP)?

Immune-mediated isolated low platelet count in absence of other etiologies

What causes immune thrombocytopenic purpura (ITP)?

Environmental exposure (medications and toxins), Infectious agents (Helicobacter pylori)

What are the clinical features of immune thrombocytopenic purpura (ITP)?

Isolated thrombocytopenia, epistaxis, petechiae, bleeding

What are the histological features of immune thrombocytopenic purpura (ITP)?

Isolated thrombocytopenia, large and well-granulated platelets, no significant dysplasia of any lineage

What is the treatment implication of type 1 heparin-induced thrombocytopenia (HIT)?

Usually, no change in heparin therapy needed

What is the treatment implication of type 2 heparin-induced thrombocytopenia (HIT)?

Heparin must be stopped, alternative anticoagulant required

What is Evans syndrome?

Combination of immune-mediated thrombocytopenia and Coombs (+) autoimmune hemolytic anemia

What is pseudothrombocytopenia?

Physiologically normal with a true normal platelet count, in vitro laboratory artifact, anticoagulant in collection tube modifies platelet surface antigens causing antibody-mediated platelet agglutination

What anticoagulants are implicated in pseudothrombocytopenia?

EDTA, Citrate, heparin, oxalate, hirudin

What are thrombotic Microangiopathies (TMAs)?

Group of disorders caused by excessive platelet activation, formation of platelet rich thrombi in small vessels

What is the treatment for TTP?

Plasmapherisis first, platelets never

What does schistocytes, low platelets and neurologic symptoms point to?

TTP

What happens when there is an ADAMTS13 deficiency?

Ultralarge vWF multimers

What is hemolytic uremic syndrome (HUS)?

Acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia

What infection causes diarrheal/infectious hemolytic uremic syndrome (HUS)?

Shiga toxin-producing bacteria (e. coli O157, Shigella dysenteriae)