PowerPoint 3 - Over and Under Production

What is polycythemia vera?

Inappropriate production of RBCs

What is the name for an inappropriate production of RBCs

Polycythemia vera

What are the causes of polycythemia vera

Primary genetic disorder or secondary to another disease

What can is the primary genetic disorders that can cause polycythemia vera?

Mutation in JAK2 gene

What disorder is this?

Polycythemia vera

Increased RBCs lead to what?

Increased viscosity

What are the symptoms of polycythemia vera?

Fatigue, shortness of breath, red or ruddy complexion, claudication (muscle cramping with exertion), stroke, pruritus (worse after hot shower), and splenomegaly

What symptoms are present in primary polycythemia?

Bleeding and peptic ulcers

Secondary causes of polycythemia vera are what?

Chronic hypoxia (COPD, congenital heart disease, sleep apnea, living at high altitudes, congenital hemoglobin abnormalities, chronic carbon monoxide exposure, and Pickwickian syndrome) and smoking

Why does low oxygen cause polycythemia vera?

Causes kidneys to release erythropoietin, which stimulates RBC production

What does erythropoietin do?

Stimulate RBC production in bone marrow

What is found in polycythemia vera labs?

CBC - Hematocrit elevated, hemoglobin elevated, platelets can be slightly elevated, WBC usually elevated, but normal RBC shape and size

Bone marrow biopsy - hypercellular

Genetic screening - positive JAK2 mutation

What would erythropoietin levels be in primary polycythemia?

Low

How do you treat primary polycythemia?

Bloodletting

How do you treat secondary polycythemia

Treat underlying cause

Supplemental oxygen (COPD)

Weight loss (too big for own good)

CPAP (sleep apnea)

What is thrombocyteosis?

High platelet count

What is the disorder with a high platelet count?

Thrombocytosis

What are the 2 kinds of thrombocytosis?

Essential and Reactive

What can cause essential thrombocytosis?

Autonomous production by bone marrow

Increased megakaryocytes

Seen in conjunction with polycythemia vera

What are the five I’s for reactive thrombocytosis causes?

Infection, inflammation, ischemia, infarction, and iron deficiency

Besides the five I”s what can cause reactive thrombocytosis?

Release of interleukin 6 (IL6), which stimulates platelet formation and release

What is more common - Essential or reactive thrombocytosis

Reactive

What is the most common symptom in thrombocytosis?

Thrombosis

What is thrombosis?

Inappropriate clot formation

What are the symptoms of essential thrombocytosis?

Asymptomatic, but can come with

Fatigue

Splenomegaly

Erythromelagia (burning in hands)

Parethesia (numbness/tingling)

What is erythromelalgia?

Burning in hands

What is erythromelalgia associated with?

Essential thrombocytosis

What are the symptoms of reactive thrombocytosis?

Symptoms of underlying disorder

Bleeding or bruising

Lymphadenopathy

Hepatosplenomegaly

Why do more platelets lead to increased bleeding?

Platelets are abnormal and less effective and are using up clotting factors that aren’t needed

How do you diagnose Essential Thrombocytosis?

By diagnosis of exlusion

What do we do and possibly see in an Essential Thrombocytosis diagnosis?

We rule out causes of reactive thrombocytosis

CBC has elevated platelets (can be over 2,000,000)

Bone marrow biopsy has increased megakaryocytes

How do we go about diagnosing Reactive Thrombocytosis?

Identify the causes

What are possibly causes of Reactive Thrombocytosis?

Inflammatory (Rheumatoid arthritis or ulcerative colitis)

Chronic infection

Iron deficiency

What is typically in a CBC of Reactive Thrombocytosis?

Platelets rarely go over 1,000,000

What do you give to treat Thrombocytosis?

Hydroxyurea

Anagrelide

Aspirin 81 mg twice daily

What does hydroxyurea help treat and do for the disease?

Thrombocytosis and reduces rapidly proliferating cells

What does anagrelide treat and what does it do for the disease?

Thrombocytosis and prevents maturation of megakaryocytes (megakaryocytopoiesis)

What does low dose Aspirin help treat and what does it do for the disease?

Thrombocytosis and treats erythromelalgia, paresthesia symptoms, and prevents clots

What are the things that cause leukocytosis?

Infection

Inflammation/autoimmune conditions

Stress response/steroids

Cancer

What is multiple myeloma

A plasma cell malignancy of bone marrow

What does multiple myeloma do?

Replaces bone marrow with localized destruction of bone and produces abnormal immunoglobulins (mostly IgG)

What is the typical showings for multiple myeloma? (Just CRAB)

Calcium is high

Renal impairment (Caused by excess immunoglobulin level and high calcium)

Anemia (healthy cells crowded out and suppresses RBC production)

Bone pain (spine, ribs, proximal bones and prone to fractures)

Besides CRAB what are other showings for multiple myeloma?

Increased infections (pneumonia and pyelonephritis)

Rouleaux formation on blood smear (“stacked coin” appearance)

Lytic lesions on x-ray

What is this and what is it a sign of?

Lytic lesion and multiple myeloma

What is used for diagnosis of multiple myeloma?

Serum and urine testing for monoclonal protein (serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP)

Bone marrow biopsy

What is the definitive diagnosis for multiple myeloma?

Bone marrow biopsy

What does Serum protein electrophoresis (SPEP) used to help diagnose and what is it used to measure?

Multiple myeloma and measures monoclonal proteins (high gamma globulins)

What does urine protein electrophoresis (UPEP) used to help diagnose and what does it detect?

Multiple myeloma and detects Bence-Jones proteins in urine

How do we treat multiple myeloma?

Stop the over production of plasma cells (chemotherapy, steroids, stem cell transplantation)

Fix the damage (Osteoporosis medications)

What is the median survival after multiple myeloma diagnosis?

7 years

What are leukemias?

Malignancy originating and spreading through bone marrow

What are the 2 types of leukemias and what are the names of the leukemias in those groups?

Acute (Acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML))

Chronic (Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML))

What are the symptoms of leukemia?

Fever

Night sweats

Weight loss

Bone pain

Splenomegaly

Fatigue

Easy bruising/bleeding

What is the most common leukemia of children?

Acute lymphoblastic leukemia (ALL) - All children get ALL

What happens in ALL?

Immature lymphocytes overwhelm healthy blood cell production

How is ALL diagnosed?

Through blood tests and bone marrow biopsy

What are the prospects for ALL?

Rapidly fatal without aggressive treatment (chemotherapy and stem cell transplantation), but successful treatment leads to remission or even a cure

What is acute myelogenous leukemia (AML)

Overproduction of myeloid cells

What is the etiology of AML?

Nothing that is clear, but prior cancer treatment, radiation or chemical exposure, family history, and previous blood disorders increase risk

What is seen in blood smear for those that have AML?

Auer rods

How do you treat AML?

Chemotherapy to induce remission

Prevent relapse with more chemotherapy and bone marrow transplantation

What is the little pink slash beside the nucleus of the middle cell, and what does that mean for this patient?

An Auer rod and he has acute myelogenous leukemia (AML)

What is chronic lymphocytic leukemia (CLL)?

Slow growing cancer of the blood and bone marrow

What is seen in patients with CLL?

Excess B lymphocyte production

What are the symptoms of CLL?

Often asymptomatic

What is the treatment for CLL?

Watch and Wait

Treat patients with symptomatic lymphadenopathy, anemia, and thrombocytopenia

What is the specific chromosomal abnormality seen is chronic myeloid leukemia (CML)?

Philadelphia chromosome

What is seen in the early phase of CML?

Increased circulating mature myeloid cells

How do you treat early phase of CML?

Tyrosine kinase inhibitor

Typically causes remission by 3 months, but survival approaches 100%

What is seen in the blast phase of CML?

Anemia and thrombocytopenia

How do you treat the blast phase of CML?

Tyrosine kinase inhibitor and chemotherapy

What is leukopenia?

Low WBC count

What is a low neutrophil count?

Neutropenia

What does neutropenia increase the risk of?

Infection

What is neutropenia associated with?

Fatal bacterial or fungal infections

What are the causes of leukopenia?

Infection (EBV/Mono, hepatitis)

Cancer

Inflammatory/autoimmune conditions (lupus)

Medications (chemotherapy, antibiotics, anti-epileptics, and substances like alcohol)

Congenital disorders

How do we treat leukopenia?

Antibiotics if patients has a fever (rarely done but fever might be only sign of infection)

Treat underlying causes

Stop offending medication

G-CSF (granulocyte colony-stimulating factor) helps bone marrow make neutrophils)

What is thrombocytopenia?

Low platelet count

What can cause thrombocytopenia?

Decreased production (bone marrow failure (cancer, radiation) and congenital disease)

Increased destruction (autoimmune destruction and medications)

What can thrombocytopenia lead to?

Hemorrhage

Contusion

Ecchymosis

Purpura

Petechiae

Hematoma

When can a spontaneous hemorrhage occur?

When you have 20,000 platelets our less

What is a hemorrhage?

Loss of blood from damaged vessel

What is a contusion?

Region of injured tissue or skin (AKA a bruise)

What is ecchymosis?

The discoloration of the skin on a bruise

What is petechiae?

Small pinpoints of bleeding beneath the skin

What is purpura?

Larger spots caused by bleeding beneath the skin

Does applying pressure cause petechiae and purpura to disapear?

No the are non-blanching

What is a hematoma?

Larger amount of mostly clotted blood outside of blood vessels

Where can a hematoma be?

Skin, brain, lungs, abdomen, muscles, etc.

How do you treat a hematoma?

it may reabsorb on own or it may require surgery to remove