Labs-elevated WBC

Low alkaline phoshatase level

High uric acid

High lactase dehydrogenase

Thrombocytosis

Philidelphia chromosome

40% asymptomatic

fatigue

wt. loss

early satiety

bruising

chronic phase evolves into acute phase

chronic phase lasts 3-5 years (indolent)

WBC elevated---few blast cells seen

asymptomatic

fever, wt. loss, worsening spleenomegaly and bone pain excelerate the phase

Effective in reducing myeloid cell numbers in pts during chronic phase.

Anemia

Infection

Bleeding/platlets

Bone pain

Lymhadenopathy

Hepatosplenomegaly and meningial involvement

Treatment is induction therapy to reduce the number of leukemic blasts to undectable level and restore normal hematopoiesis.

Consilidation therapy

Hallmark is pancytopenia- (all WBC, RBC and platlets gone)

Anemia

Splenomegaly is massive

Cells present on bld smear and especially in bone marrow biopsy

Prognosis is open ended

Hallmark is isolated lymphocytosis (above 45%)

Dz of older people, median 65 yrs

WBC >20K (up to several hundred thousand)

Early indolent requires no therapy

About 90% are from B-cell lymphocytes

Peak incidence btween 20-40 yrs

Indolent to aggressive dz

1/3 of aggressive are curable with chemo

Diffuse, painless, persistent lymphadenopathy

Extralymphatic sites are the gastrointestinal, skin, bone and bone marrow.

Bimodel, most common in 15-45 yrs (more common in men) and after 65 yrs

Enlargement of of lymphoid tissue, spleen and liver and presence of Reed-Sternberg cells.

Cervical, supraclavicular and mediastial lymphadenopathy

Nodular sclerosis seen in young women

Stage A indicates a lack of constitutional symptoms

Fever, wt. loss and drenching night sweats

Rapid proliferation

Ann Arbour staging used

Puritis  and headache are NOT a symptom

****

Chemo cures 50% with advanced stage

Radiation therapy cures 90% of stage 1

Adriamycin, bleomycin, vinblastne, and decarbazine (ABVD) have fewer side effects than

Nitrogen mustard, vincristine, procarbazine and prednisone (MOPP)

WBC

Diff count

RBC

RBC indices (MCV, HCH, MCHC)

Hematocrit (HCT) and Hemoglobin (Hgb)

Platlet count

Bld smear for WBC diff, RBC morphology and platlets

Retiuculocyte count

• Greater than 21 yrs – 4.5 to 11,000
• 8-21 yrs – 4.5 to 13,500
• 4 yrs – 5 to 15,000
• 1 yr – 6 to 18,000
• 14 days – 5 to 20,000
• Birth – 9 to 30,000

•  Less WBC than the range given for an age group

Most populous WBC that earns their living by phagocytosis

Consist of the band and segmented types

In stress situations an increase in bands, i.e., “shift to the left” can be seen in the blood

WBC Morphology

Neutrophils(PMN)

Not a “granulocyte”

They turn into Macrophages that present foreign antigens to the immunocompetent lymphocytes

They also are capable of phagocytosis but trade off killing power

Monocytes

Capable of ameboid motion and phagocytosis

A grandulocyte that is increased in parasitic infestations and allergic conditions and may have a critical function in mitigating allergic responses

Eosinophils

 Another granulocyte with the distinction of being the least numerous

Has a reciprocal relationship with the mast cell--

Mast cells go up during allergic reactions

Basophils

 The central cell of the immune system

They mediate the adaptive immune response, providing specificity to the immune system

Two major functional classes: B cells and T cells

When activated they can transform into “atypical or viral lymphocytes”

Lymphocytes

Mild: 1000-2000/uL

Moderate: 500-1000/uL

                            Severe: < 500/uL----Patient in danger of severe infection, must start antibiotics and admit to the hospital

Neutropenia

The main oxygen-carrying pigment and is distribute in erythrocytes

Called the packed cell volume or PCV

It is a measure of the total volume of the erythrocytes relative to the total volume of whole blood in a sample

Hematocrit

Men – 42 to 52%

Women – 37 to 47%

Normal adult values for hematocrit

Men – 14 to 18 g/dl

Women – 12 to 16 g/dl

Normal adult values for hemoglobin

Rule of thumb: Under normal conditions the hemoglobin is 1/3 the hematocrit

Normal adult male – 4.3 to 5.9

Normal adult female – 3.5 to 5.5

 Red Blood Cell Count

The amount of RBC’s in one cubic millimeter of blood

An increased RBC count may include:

Polycythemia vera--RBC mass is increased

                Vigorous exercise-By increasing O2 demand, O2 deficit

High altitude exposure

Almost always manifested by a decreased hemoglobin and frequently accompanied by a decreased hematocrit and red cell count-

• Anemia (the reduction in the oxygen carrying capacity of the blood)

The range of diagnostic possibilities for anemia can be reduced greatly by obtaining both a

Reticulocyte count

Peripheral blood smear

****

An elevated reticulcyte count means

peripheral RBC destruction or blood loss

A low or normal reticulocyte count means

failure of RBC production and a hypoproliferative anemia is present

Macrocytic –B12 or Folate deficiency

Normochromic-Normocytic –Seen in erythropoietin failure, e.g., Renal failure, chronic inflammation

Microcytic-Hypochromic –Iron deficiency, Thalassemia syndromes

Hypoproliferative Anemia-three catagories

Idiopathic, systemic illness, drug use

Immune Hemolysis

Heart valves, obstructed vessels, hemangiomas

Mechanical Hemolysis

Immune Hemolysis:

Idiopathic, systemic illness, drug use

Mechanical Hemolysis:

Heart valves, obstructed vessels, hemangiomas

Sickle Cell Anemia

Glucose-6-phosphate dehydrogenase deficiency (G6PD)-Pts don’t want to go overseas with this.

Causes of Red Cell Destruction

• Mean Corpuscular Volume (MCV)--Average size of the RBC

The most clinically useful indice

• Mean Corpuscular Hemoglobin (MCH)--The amount of hemoglobin per cell
• Mean Corpuscular Hemoglobin Concentration (MCMC)--A percentage measure of how much of the RBC consists of hemoglobin

• MCV > 100 fL
  • e.g., B-12 &/or Folate deficiency

Macrocytic anemia

• MCV < 80 fL
  • e.g., Thalassemia(minor), Iron deficiency

Microcytic anemia

• MCV 80 to 100
  • e.g., Sudden blood loss, Renal failure

Normocytic anemia

• Mean Cell Hemoglobin Concentration is decreased

Iron deficiency anemia, lead poisoning

• Mean Cell Hemoglobin Concentration is increased

Hereditary Spherocytosis

***Variability in cell shape

Poikilocytosis

**** 

Variability in cell size

Anisocytosis

•  
  • Seen in Thalassemias

Target cells-RBC seen on peripheral smear

• Loss of biconcave shape with no central pallor seen in ________.

Spherocytosis-RBC seen on smear

• RBC frags (heart valve, DIC)

Schistocytes

• Are masses of denatured hemoglobin seen after splenectomy
  • The spleen removes all intraerythrocyte inclusions
• Seen in thalassemias, and early in the course of hemolysis in G6PD

Heinz bodies

• Persons whose platelets are defective in number or function experience petechiae

Primary Hemostasis

• It is found in the intestinal mucosa, spleen, bone marrow, reticulocytes, and liver, and regulates iron storage and transport of iron from the intestinal lumen to plasma
• The first biochemical marker for iron deficiency
• Measurements are useful for monitoring and discontinuing iron therapy

• Serum Ferritin

Is usually measured along with:

• The iron-binding capacity (total iron-binding capacity; TIBC) in the work-up of:
  • Anemias
  • Iron overload
  • Hemochromatosis
  • Thalassemia

• Serum Iron

• The serum iron is decreased
• TIBC is increased
• Serum ferritin is decreased

Iron deficiency anemia

• The capacity of serum transferrin to bind to iron and is obtained by this test
• Normal 240-360 ug/dl

Total Iron-Binding Capacity(TIBC)

• Male: up to 15 mm/hr
• Female: up to 20 mm/hr
• Child: up to 10 mm/hr

• Erythrocyte Sedimentation Rate

Persons whose platelets are defective in number or function experience petechiae

They are also unable to stem bleeding from injury to blood vessels

Primary Hemostasis

• Hemoglobin in red cells – about 2.5 g-(red cell mass)
• Iron containing proteins, such as myoglobin, cytochromes, and catalase – 400 mg
• Bound to Transferrin in Plasma – 3 to 7 mg

Normal iron content is about 3 to 4 g. It exists in the following forms

It is found in the intestinal mucosa, spleen, bone marrow, reticulocytes, and liver, and regulates iron storage and transport of iron from the intestinal lumen to plasma

The first biochemical marker for iron deficiency.

Measurements are useful for monitoring and discontinuing iron therapy

Serum Ferritin

does not indicate that the body iron stores have been replenished

A normal hemoglobin

Normal ranges: Male- 20-300 ng/ml, Female- 20-120 ng/ml

Serum Ferritin levels

• Anemias
• Iron overload
• Hemochromatosis (Dz-too much iron in system and gets into other organs)
• Thalassemia-major one is worse

The iron-binding capacity (total iron-binding capacity; TIBC) in the work-up of

Serum iron is usually measured along with

•  
  • The iron-binding capacity (total iron-binding capacity; TIBC)

• The serum iron is decreased
• TIBC is increased-the bucket of iron is decreased so the capacity is increased. 
• Serum ferritin is decreased

In Iron deficiency anemia

• The capacity of serum transferrin to bind to iron and is obtained by this test

Total Iron-Binding Capacity(TIBC)

• Normal 240-360 ug/dl

Total Iron-Binding Capacity(TIBC)

• With normal iron stores and protein metabolism, _______ is usually 30 to 35% saturated

• Male: up to 15 mm/hr
• Female: up to 20 mm/hr
• Child: up to 10 mm/hr

Erythrocyte Sedimentation Rate

• A nonspecific test use to detect illnesses associated with:
  • Acute and chronic infection
  • Inflammation (collagen-vascular disease)
  • Advanced neoplasm (cancer)
  • Tissue necrosis or infarction

Erythrocyte Sedimentation Rate

a measurement of the rate which the RBCs settle in saline solution or plasma over a specified time period

ESR

ESR will be increased in

inflammatory, neoplastic, infectious, and necrotic diseases

provides the same information as an acute-phase reactant (ex; high cholesterol) protein

ESR

Normal Findings:

• < 1.0 mg/dL

CRP (C-reactive protein)

 levels do not consistently rise with viral infections.

 Is an abnormal protein produced primarily by the liver during an acute inflammatory process, for example, myocardial infarction

CRP (C-reactive protein)

The synthesis of  _______ is initiated by antigen-immune complexes, bacteria, fungi, and trauma

CRP (C-reactive protein)

correlates with peak levels of the MB isoenzymes of creatine kinase, but _____ peaks occur 18 to 72 hours later

CRP (C-reactive protein)

Levels are not elevated in patients with angina--have to have necrosis/inflammation

CRP (C-reactive protein)

________ are caused by abnormalities of:

Platelets and/or Blood vessels

Coagulation factors

Hemostatic defects

• Present with more prominent bleeding in deep tissue and atraumatic hemarthroses (bleeding into joints)

Coagulation factors

tests to determine why a pt is  bleeding

Bleeding Time

PT, extrinsic cascade system (PET)

PTT, intrinsic system (TIT)

• Normal in coagulation disorders

• Bleeding Time

• The conversion of fibrinogen (factor I) to fibrin
• It is mediated by thrombin (factor IIa) which is generated from prothrombin (factor II)

The above conversion is mediated by factor X (Xa)

This final step can be generated by the

• intrinsic or extrinsic pathway
• Is vitamin K dependent-associated with extrinsic pathway of coagulation

Coagulation Cascade

• A true cascade initiated by the exposure of factor XII to an unknown mechanism
• Followed subsequently by kallikrein during the contact phase

Intrinsic pathway

• Involves factor VII
• Factor VII complexes with calcium and a tissue factor (TF

Extrinsic pathway

Setting off a final, common pathway that ends with formation of the fibrin clot

• Factor X

measures the ability to form a fibrin clot by the intrinsic pathway

PTT

measures the ability to form a fibrin clot by the extrinsic pathway

PT

used to monitor Heparin therapy

PTT

a measure of all of the blood factors except factor VII

Heparin antidote is

Protamine sulfate***

Bleeding can result from

• Thrombocytopenia (decreased platelet count)
• Abnormal platelet function

a “Bleeding Time” should be performed when

a patient has clinical symptoms of a bleeding disorder, and has a normal platelet count and has a normal PT and PTT

If the “Bleeding Time” is prolonged in a patient with a normal platelet count what could be the cause?

an abnormality of the platelets or the blood vessels

• Drugs can cause thrombocytopenia through marrow toxicity or platelet destruction

Drug-Induced Thrombocytopenia

• Alcohol –marrow toxicity
• Thiazide diuretics – marrow toxicity
• Quinidine and Quinine – platelet destruction
• Heparin – platelet destruction through platelet antibodies or platelet aggregation

Drugs can cause thrombocytopenia

• Antiplatelet antibodies have been implicated
• The patient presents clinically with petchiae and purpura, may be septic
• Normal bone marrow w/normal or increased megakaryocytes

Immune Thrombocytopenic Purpura (ITP)

Patient presents with deep-tissue bleeding-(like joint bleeding)-coagulation cascade

• In the absence of skin and mucous membrane petechiae
• The platelet count is normal

Coagulation disorders

Vitamin K deficiency is the most common

Factors II, VII, IX, X are made in the liver and require vitamin K for synthesis

A prolonged “PT” is the first laboratory evidence of vitamin K deficiency

Prothombin time will be increased

Acquired Coagulation Disorders

Vitamin K deficiency can be caused by:

• Intestinal malabsorption
• oral anticoagulants
• liver failure (grim prognosis)

The most common severe bleeding 

Sex linked recessive trait

Results in a deficiency of factor VIII

This condition can be mild, moderate or severe

Hemophiliacs most often enter the hospital because of hemarthrosis (blding in joint space-painful)

Therapy for ongoing bleeding involves replacement of factor VIII

Inherited Coagulation Disorders

Hemophilia A

The most common congenital disorder of hemostasis

A coagulation factor VIII problem

Epistaxis, is the most common manifestation

Dx by prolonged bleeding time and PTT

Ristocetin (antibiotic)-induced platelet aggregation is negative 

Treatment – DDAVP or factor VIII concentrate

Von Willebrand’s Disease (vWD)

Widespread activation of the coagulation system

Can be either an explosive and life-threatening bleeding disorder  or a relatively mild or subclinical disorder

Most frequently associated with

     Obstetric catastrophes

              Metastatic malignancy

     Massive trauma

     Bacterial sepsis

Disseminated Intavascular Coagulation (DIC)

potent thrombogenic stimuli producing deposition of small thrombi and emboli throughout the microvasculature

produces a presence of circulating thrombin

Disseminated Intavascular Coagulation (DIC)

• Cleave fibrinogen to a fibrin monomer
• Stimulate platelet aggregation
• Activate factors V and VIII
• Release plasminogen activator

The effects of thrombin

finally inactivates factors V and VIII

 Is generated from the plasminogen activator

Cleaves fibrin

Plasmin

leads to schistocytes** (fragments of RBC) detected on peripheral blood film

Microangiopathic hemolysis

The PT and PTT are prolonged, and the thrombin time is also prolonged because of decreased levels of fibrinogen

• The above effects lead to small-vessel emboli, thromboses, severe anemia, and tissue bleeding

Disseminated Intavascular Coagulation (DIC)

Widespread activation of the coagulation system

Bone marrow disease characterized by an absence of stem cells secondary to toxic exposure (ie. Chronic drug use, etc.)

All myeloid (derived from the bone marrow) cell lines are involved, with a resultant Pancytopenia

Bone Marrow Failure also called Aplastic Anemia

Management is discontinuation of potential exposure; marrow transplant

~50% mortality w/ therapy 

There are no abnormal cells on the peripheral smear

Bone Marrow Failure also called Aplastic Anemia

• Fatigue
• Weakness
• Epithelial changes such as brittle nails and atrophic tongue
• Many are asymptomatic

Iron Deficiency Anemia

The most common form of anemia in the United States

• The iron deficiency is cause by blood loss and the loss of the iron component

• A smear showing hypochromia  and microcytosis  is adequate for the diagnosis

•  
  • Abnormally low levels of ferritin
  • Low serum iron levels
  • Elevated total iron-binding capacity (TIBC)

Iron Deficiency Anemia

• Oral iron in the form of ferrous sulfate 325 mg PO TID on a empty stomach
• Vitamin C will increase absorption
• Treatment is usually for 6 months to replace iron stores
• Reticulocytosis occurs 7 days after appropriate treatment-seen from reticulocyte count to see if therapy is working
• After ~ 3 wks, the hemoglobin level increases several grams

Iron Deficiency Anemia

Diminished iron utilization by the bone marrow

Therefore, inadequate amounts of iron are available to the bone marrow for RBC formation despite adequate body stores

Inflammatory cytokines are thought to be involved

This inflammatory state impairs marrow response to erythropoietin

Anemia of Chronic Disease

• Low serum iron
• Hemoglobin of 8 – 10 g/dL
• Low TIBC-that's good. The capacity to fill up is low.
• Normal or increased serum ferritin-has good storage of iron

Anemia of Chronic Disease-labs

• Correction of underlying disorder
• Erythropoietin has been shown to be effective for renal failure, cancer, and inflammatory disorders such as rheumatoid arthritis

Anemia of Chronic Disease

This reduction in synthesis results from failure to incorporate heme into protoporphyrin to form hemoglobin

A bone marrow biopsy will reveal ringed sideroblasts

• Cells with iron deposits (in the mitochondria) encircling the red cell nucleus

Sideroblastic Anemia

• Any anemic patient who reveals marked abnormalities on blood smear, such as
  • Microcytosis and Hypochromia
  • Poikilocytosis (bizarrely shaped RBCs)

• Thalassemias

There is irreversible neurologic damage if uncorrected

Clinical features:

Sore tongue (glossitis)

Stocking-glove paresthesia

loss of fine touch and vibratory sensation

Clumsiness

ataxia

Vitamin B12 Deficiency Anemia

Pernicious anemia is the most common cause

• MCV > 100 (possible to have a normal MCV)
• Reticulocytes are decreased
• Anisocytosis and poikilocytosis on smear
• Positive Schilling test for pernicious anemia

Vitamin B12 Deficiency Anemia

• Normal 150-350 pg/mL

Vitamin B12 Deficiency Anemia

Treatment 

For life

• IM injections of 100 ug of vitamin B12 daily for one week, then
• Weekly for one month, then monthly for life

A reticulocytosis occurs in 5-7 days with a normalizing hematologic picture in ~2 months

Vitamin B12 Deficiency Anemia-treatment

Macrocytic anemia with the MCV > 100

Reticulocytes are decreased

This disorder does not cause neurologic deficits

Folic Acid Deficiency

• Sore tongue (glossitis)
• Poorly localized abdominal pain
• Intermittent constipation
• Diarrhea

Causes of Folic Acid Deficiency

Hypersegmented polymorphonuclear leukocytes (PMN) are pathognomonic for megaloblastic maturation

Howell-Jolly bodies are typical

Red blood cell folate levels are decreased

Folic Acid Deficiency

• Daily requirement is 50 – 100 ug
  • Tx is 1mg per day
  • Should see correction in two months
  • 5-7 days will see reticulocytosis
• Alcohol should be avoided
• Malabsorption, if present, must be diagnosed and treated

Folic Acid Deficiency

• Defined as sickling of cells causing vaso-occlusive disease with bone, lung, renal infarctions, often precipitated by exposure to cold and infection
• It may be difficult to differentiate abdominal pain from a sickle crisis from the pain of a surgical abdomen
• May develop Priapism

Sickle Cell Anemia

• Fever
• Increased bilirubin

Sickle Cell Anemia

• Occurs in 40% of patients with sickle cell anemia
• Characterized by “pleuritic” chest pain, fever, hypoxia, cough, dyspnea, rales, and crackles
• Usually there is a rapid decrease in Hb with increased platelets and WBC
• Major source of mortality in those with sickle cell disease (15% of deaths in adults)
• Must differentiate from pneumonia***

Acute chest syndrome

• Causes hemoglobin to drop from 3 to 6 g/dl
• These patients may also have aplastic crisis in response to parvovirus B19

Acute splenic sequestration syndrome

• May have hematuria
• Trouble concentrating urine
• Very rarely a sickle crisis

Sickle trait

• Pain control (such as IV morphine)
• Hydration (IV fluids)
• Transfusion with a Hb < 5 g/dL
• Admission as required to treat:
  • Infection
  • To maintain hydration
  • Parenteral analgesics

Treatment-

Sickle Cell Anemia

• CBC with differential, platelet count
• Mean corpuscular volume (MCV). In hemolysis, elevated MCV reflects reticulocytosis
• Serum ferritin (estimate of Fe stores)
• TIBC (mmol/L)

Laboratory evaluation of Anemia

• A count that is normal or low (in the face of anemia) is suggestive of the inability of the bone marrow to respond to anemia (marrow failure)
• A count that is increased is indicative of acute blood loss or hemolysis with a marrow that is able to respond

Laboratory evaluation of Anemia

Reticulocyte count

• If the count is low or normal (“marrow failure”), the MCV is helpful in diagnosing.
• The MCV is either normocytic at 80 to 100 femtoliters (fl), microcytic < 80 fl, or macrocytic > 100 fl

Laboratory evaluation of Anemia

• There is hemolysis in the RBC after exposure to substances that cause oxidative stress, including:
• Drugs – sulfonamides, nitrofurantoin, salicylates, vitamin C, quinine, quinidine, dapsone
•  Fava beans
• Infections 
• DKA and renal failure

G6PD Deficiency

• Check levels when reticulocyte count is normal
• If checked after acute hemolysis, those cells surviving in the circulation and the young reticulocytes may have a normal _____.

G6PD Deficiency diagnosis

G6PD

• May develop renal failure secondary to hemolysis
• Maintain hydration and withdraw offending agents

G6PD Deficiency treatment

A congenital defect of the main component of the erythrocyte cell membrane

The membrane becomes abnormally permeable to sodium, resulting in thickened and almost spherical RBC’s

The RBC is fragile and susceptible to spontaneous hemolysis, with decreased survival in the circulation

Hereditary Spherocytosis

• Chronic anemia with reticulocytosis
• Episodes of mild jaundice due to hemolysis
• Acute crises with gallstones, fever, and abdominal pain

Hereditary Spherocytosis

Patients w/ significant hemolysis should receive folate supplementation

Patients w/ significant hemolysis should receive folate supplementation

• Symptoms –
  • DOE
  • Palpitations
  • Angina pectoris
  • Lightheadedness
  • Syncope
  • Anorexia and Tinnitus

Hemolytic Anemia

Patients usually have the classic SxS of anemia with this disorder

• Signs –
  • Pallor of skin and mucous membranes
  • Mild tachycardia
  • Peripheral edema
  • Systolic ejection murmurs from increased flow

Hemolytic Anemia

• Fever, chills, tachycardia, tachypnea, backache, and hemoglobinuria
• The hemoglobinuria can precipitate renal failure
• Also, patients with the above may develop cholelithiasis secondary to pigment stones

Manifestations of Hemolytic crisis which is rare

The above disease is an acquired hemolytic anemia

It is due to immunologic destruction of RBCs mediated by autoantibodies directed against antigens on the patient’s RBCs

Cold Agglutinin Disease

IgM antibodies react with antigens on the surface of the RBC only at temperatures below that of core temperature of the body

Cold Agglutinin Disease

• Often there is a normochromic-normocytic profile
• Generally elevated indirect bilirubin with normal direct bilirubin
• Hemoglobinuria may be present

The direct Coombs test  is positive

• There is mild anemia and a reticulocytosis and spherocytosis

Cold Agglutinin Disease

A 65 yr presents with progressive fatigue, symptomatic lymphadenopathy, anemia and thombocytopenia with isolated lymphocytes, and a WBC of 40,000.

Symptoms include:

• Urticaria
• Pain in the lumbar region
• Flushing
• Headache
• Precordial pain SOB, N/V, rigors, pyrexia, or hypotension, DIC, and Jaundice

Transfusion Reaction

Transfusion Reaction

Treatment:

• Stop the transfusion immediately and draw blood from the patient to check for free hemoglobin in the plasma, if present your job is to prevent acute tubular necrosis by vigorous hydration with IV fluids
• Furosemide, corticosteroids, and antihistamines as necessary
• Epinephrine for severe shock

Transfusion Reaction

given to raise the hematocrit levels in patients with anemia or to replace losses after acute bleeding episodes

Blood Transfusions

Is never absolutely necessary, since RBCs, plasma, and fresh platelets are available separately.

The major indications for use of _______ are cardiac surgery or massive hemorrhage when more than ten units of blood are required in a 24-hour period

Fresh whole blood

• RBCs can be frozen and stored for up to 3 years
• Major use is to maintain a supply of rare blood

Frozen blood

• Used for patients scheduled for elective surgery
• These patients may donate their own blood for autologous transfusion
• These units may be stored for up to 35 days

Autologous packed red blood cells

• Only the ABO and Rh systems are tested prior to all transfusions

Compatibility testing

• Only ________ should be given to avoid transfusion of donor plasma containing anti-A or anti-B antibodies

packed cells

• The other important antigen routinely tested for is the ___________ of the Rh system

• The recipient’s and the donor’s blood are cross-matched to avoid

• A recipient whose RBCs lack D and who receive D-positive blood may develop anti-D antibodies that can cause

• Anyone who lacks the A or B red blood cell antigens has ________ against the missing antigen or antigens in his or her plasma

This condition sets the patient up for thrombosis

The most common cause is malignancy

Other conditions that may precipitate this are:

• Ulcerative colitis, Crohn’s disease, MPD, Estrogen therapy, Pregnancy, Lupus anticoagulant, Heparin induced thrombocytopenia, Anticardiolipin antibodies

Hypercoagulability

An increased RBC mass in the peripheral blood · May be primary or secondary ○

Increased levels of erythropoiesis in response to physiologic stimuli Primary a clonal stem cell disorder of unknown origin It is characterized by erythrocytosis associated with other hematopoietic abnormalities.

Lymphocytes

Igm M protein=thick blood

65 yrs old

Weakness, fatigue, bleeding nose, gums

Severe normocytic, normochromic anemia

Rouleaux formation, ESR increased

Chlorambucli

Waldenstroms macroglobinema

Bone marrow=plasma cell-cells over populate bone

Impairs bld production-anemia

Damage to normal structure of bone- bone pain, rib pain

Damage to kidney

Chemo

Stem cell transplantation

Multiple myeloma=BONE

Bleeding nose, mouth, petechiea, purpura

Thrombocytopenia

I=immune

T=thromocytopenia-low platelets

P=purpura-bleeding

I=immune

T=thromocytopenia-low platelets

P=purpura-bleeding

Bld clotts

Low platelets=thrombocytopenia

Neuro sxs=HA, confusion, aphasia

HIV

Febrile

Microangiopathic with fragments RBC on bld smear

Lg vol. plasmapheresis or splenectomy

TTP

Hemolysis and renal failure combined

Sxs=vomiting, diarrhea preceed anemia and renal failure

Bleeding and dark colored urine

Oliguria or anuria

Decreased hemaglobin with extreme BUN and Creatine

Lg Vol. plasmapheresis

Hemolytic Uremic Syndrome  "0157"

Deficiency of factor VIII:C

X link recessive-males-mother carries

Bleeds in the joints, muscles, GI tract

Trauma, spontaneous

PTT prolonged

Prothrombin time, bleeding time and fibrinogen level normal

vWF are normal

TX=usion of factor VIII concentrates

Mild-DDVAP

Hemophillia A

Christmas Disease/factor IX

PTT prolonged and factor IX reduced

TX=factor IX concentrates

Hemophillia B

Most common congenial d/o

Autosomal dominant

Deficient vWF

Bleeding of nose, gums, Menorrhagia, GI

Dx=abnormal vWF, normal platelets, bleeding time prolonged

Desmopressin acetate, Tranexamic acid used before surgery/denist

Tx-none-avoid aspirin

Von Willebrand Dz

Vitamin K deficiency responds rapidly to subcutaneous vitamin K, and a single dose of 15 mg will completely correct laboratory abnormalities in 12- 24 hours

thrombosis

Contrast conditions that cause stasis of blood flow (ie. being post-op) versus systemic disorders that cause a general increase in the risk of thrombosis (See next slide)

cause is malignancy

Other conditions that may precipitate hypercoagulability are:

Ulcerative colitis, Crohn’s disease, MPD (look this up if you don’t remember), Estrogen therapy, Pregnancy, Lupus anticoagulant, Heparin induced thrombocytopenia, Anticardiolipin antibodies

Hypercoagulability

immediate or delayed

Clinical features include a hemolytic shock phase occurring after a few milliliters of blood have been transferred or up to 2 hours later

Symptoms include:

Urticaria

Pain in the lumbar region

Flushing

Headache

Precordial pain SOB, N/V, rigors, pyrexia, or hypotension, DIC, and Jaundice

Oliguric phase

Renal tubular necrosis and acute renal failure

Diuretic phase

Transfusion Reaction

Hgb synthesis is reduced

-failure to incorporate heme into protoporphyrin to form Hgb

-ringed sideroblasts on biopsy

Sideroblastic Anemia

microcytosis and hypochromia

-poikilocytosis

Thalassemia

-pernicious anemia is most common cause

-lack of intrinsic factor causing failure to absorb B12 from GI tract

-irreversible neuro damage if uncorrected

-sore tongue, stocking glove paresthesia, loss of fine touch and vibratory sensation, clumsiness, ataxia

-MCV>100, low retics, anisocytosis and poikilocytosis

-positive Schilling test

Vit B12 Deficiency

-MCV>100

-low retics

-sore tongue, poorly localized abd pain, constipation, diarrhea

-hypersegmented PMN leukocytes are pathognomonic for megaloblastic maturation

-Howell-Jolly bodies

-avoid alcohol

Folic Acid Deficiency

abnormal Hgb S

-sickling of RBC’s causes vaso-occlusive disease

-if temp >38, state broad spectrum antibiotics

-increased bilirubin – due to RBC destruction

-acute chest – CP, fever, hypoxia, cough, dyspnea, rales, infiltrates, rapid decrease in Hgb with increased platelets and WBCs

-may have aplastic crisis in response to parvovirus B19

G6PD

Sickle Cell Anemia

-x-linked d/o in AA and Mediterranean

-hemolysis in RBC’s after exposure to substances that cause oxidative stress

-drugs, fava beans, infections, DKA, renal failure

-check G6PD levels when retics are normal

-may have normal G6PD if checked after acute hemolysis

-may develop renal failure secondary to hemolysis

G6PD

absence of stem cells secondary to toxic exposure

-pancytopenia

-all myeloid cell lines involved

-bone marrow transplant

-no abnormal cells on smear

Aplastic Anemia/Bone Marrow Failure

-epithelial changes like brittle nails and atrophic tongue

-hypochromia and microcytosis

-very low ferritin, low iron, high TIBC

Iron Deficiency Anemia

-plentiful iron but diminished iron utilization by bone marrow, therefore inadequate amounts of iron are available to the bone marrow for RBC formation despite adequate body stores

-inflammatory cytokines

-impairs marrow response to epo

-low serum iron, Hgb 8-10, low TIBC, norm to inc serum ferritin

-epo can help

Anemia of Chronic Disease

-congenital defect of main component of erythrocyte cell membrane

-membrane becomes abnormally permeable to Na resulting in thickened and almost spherical RBC’s

-RBC is fragile and susceptible to spontaneous hemolysis

-chronic anemia with reticulocytosis, mild jaundice, acute crises with gallstones, fever, and abd pain

-pts have exacerbations during infections – these pts need folate

Hereditary Spherocytosis

-classic SxS of anemia

-fever, chills, skin pallor, mild tachy, peripheral edema, systolic ejection murmurs from increased flow

-hemoglobinuria can cause renal failure

Hemolytic Anemia

-acquired hemolytic anemia

-immunologic destruction of RBC’s mediated by autoantibodies directed against antigens on the pts RBC’s

-IgM antibodies react with surface antigens at temps below core temp

-normochromic-normocytic

-elevated indirect bilirubin and normal direct bilirubin

-direct Coombs positive

-mild anemia with reticulocytosis and spherocytosis

-destruction of RBC’s due to fixation of complement, normal RBC’s have surface proteins that protect them from effects of complement

-large numbers of complement-activation units must be fixed onto the RBC surface for lysis of cell to occur

Cold Agglutinin Disease

-increased RBC mass

-primary – stem cell defect

-secondary – increased levels of epo in response to physiologic stimuli

-erythrocytosis associated with other hematopoietic abnormalities

-primary clonal stem cell d/o

-diagnosis by low epo and by ability of in vitro erythroid colonies to proliferate independent of epo

-pruritis after bathing, HA, visual problems, mental clouding

-occlusive vascular events are common as well as hemorrhagic events (b/c of abnormal platelet function)

-may present with GI bleeds – NSAIDS should be used

-chronic and progressive

-treatment – intermittent phlebotomy, low dose chemo drugs

Polycythemia Vera

-cytopenias with hypercellular bone marrow

-abnormalities in 2 or more hematopoietic cell lines

-adequate progenitor cells but ineffective hematopoiesis

-d/o can evolve into AML

-maybe splenomegaly

-MCV norm, macro-ovalocytes on smear, retics low, WBC norm or low, platelets norm or low

-ringed sideroblasts

-<20% blasts, while AML has >20% blasts

-neutropenia is common

-bone marrow transplant (curative) or azacitidine

-fatal

Myelodysplastic Syndromes

-increased granulocytic cell line

-erythroid and platelet hyperplasia

-splenomegaly

-Philadelphia chromosome

-high WBC, low Alk Phos, High uric acid, High LDH, thrombocytosis

-chronic phase that evolves to acute blast crisis

-death in weeks to months

-chemo, marrow transplant

CML

isolated lymphocytosis WBC >20,000

-early disease requires no therapy

-fatigue, lyphadenopathy, anemia, thrombocytopenia   

-old people

-young pt with CLL – bone marrow transplant

CLL

anemia, bone pain, lymphadenopathy, hepatosplenomegaly and meningeal involvement

-induction therapy – reduces number of leukemic blasts to undecteble levels and normal hematopoiesis

-consolidation therapy – eliminates further leukemic cells

-intensification therapy – eliminates cell with potential primary resistance to induction regimen

-maintainence therapy – prevents disease relapse

-adults

AML

-anemia, thrombocytopenia

-massive splenomegaly

-hairy cells on smear and biopsy

-accumulation of neoplastic B cells in marrow, blood and spleen

-no immediate therapy for asymptomatic pts

-progressive disease pts need to have therapy

HCL

-arise from cells living in lymphoid tissue

-B lymphocytes

-indolent lymphomas tend to convert to aggressive disease

-1/3 of aggressive lymphomas are curable with chemo

-painless lymphadenopathy! – need to bo biopsied

-chemo and bone marrow/stem cell transplant

Non-Hodgkin’s Lymphoma

-Reed-Sternberg cells!, enlargement of lymphoid tissue, spleen and liver

-bimodal presentation, 15-45 and >60

-lymphadenopathy, nodular sclerosis

-stage A – lack of symptoms

-stage B – poorer prognosis

-drenching night sweats, fever weight loss, hypermetabolic state

-hyperproliferation of B lymphocytes

-chemo, radiation, and drugs

Hodgkin’s Lymphoma

-proliferation of plasma cells in marrow NOT in lymph nodes

-lymphogenous tissues, lymph glands, marrow, Peyer’s patches

-produce gamma globin

-bone pain! In back and ribs

-multiple and osteolytic causing osteolysis and sometimes osteoblastic response

-hypercalcemia

-hypogammaglobulinemia and granulocyte inhibition – bacterial infections!

-neuro symptos – hyperviscosity, cryoglobulins and amyloid deposition in nerves

-anemia – inhibition of epo

-bone marrow containing 10% plasma cells OR plasmacytoma plus at least one of

-M protein in serum, M protein in urine, Lytic bone lesions

-protein electrophoresis to be done

->70 – chemo, melphalan and prednisone, <65 – peripheral stem cell transplant

-pts will relapse

Multiple Myeloma

A 58-year-old man who smoked heavily (80 pack-year) {he has lung ca} complained of hemoptysis and weakness. Wheezing was noted over the right thorax. Hematologic indices were: hemoglobin level, 10 g/dL; MCV, 80 fl; MCHC 33 g/dL; RDW, 13%; red blood cell count, 3.3 million/uL; white blood cell count, 6800/uL; and platelet count, 350,000/uL. The serum ferritin level was 120 ug/L and transferrin receptor level was 4 mg/L (normal, 2 to 9 mg/L)

What is the anemia in this case?

A 60-year-old woman who was a native of India had had mild anemia all her life and sought an explanation for her condition. Physical examination revealed no splenomegaly. Her hematologic indices were: hemoglobin, 10.5 g/dL; MCV, 56 fl; MCHC, 32 g/dL; RDW, 14%; RBC count, 8.2 million/uL; WBC, 8000/uL; platelet count, 240,000/uL

Although the patient had been anemic since childhood, she had had no symptoms of anemia

The blood smear revealed microcytic RBCs, plentiful target cells, and little heterogeneity

The MCV was very low. The serum ferritin level was 250ug/L, reflecting ample storage iron. The serum transferrin receptor level was elevated (14 mg/L)

What is the diagnosis for the patient from India?

Thalassemia

A 58-year-old man presented with weakness, dyspnea, pallor, and mild jaundice. His liver measured 11 cm (hugh)and his spleen was felt 2 cm below the left costal margin. Other than slight jaundice, he showed no symptoms of liver disease. Hematologic indices were: hemoglobin level, 7 g/dL; MCV, 110 fl; MCHC, 38 g/dL; RDW, 20%; RBC count, 2.6 million/uL; WBC count, 10,000/uL; and platelet count, 452,000/uL.

The patient had elevated serum bilirubin and LDH with normal serum albumin levels

Blood smear revealed many blue, larger RBCs, many deformed RBCs, and a few spherocytes

The MCV was high

Note: The first step in the evaluation of a patient with an elevated MCV is to obtain a reticulocyte count, his was 8%

The absolute reticulocyte count was 208,000/uL

In the setting of severe anemia, this level of reticulocytosis reflects a brisk marrow response to the peripheral destruction of RBCs

This patient’s blood smear is consistent with the diagnosis of:

Hemolytic Anemia

Once the diagnosis of hemolytic anemia was confirmed, what test should be ordered next and why?

Direct Coombs test to determine whether the hemolysis was caused by autoimmunity

A 75-year-old women complained of weakness, easy fatigability, and dyspnea on exertion. She appeared frail and pale, and ecchymoses were evident on her arms and legs. Hematologic indices were: hemoglobin level, 6 g/dL; MCV, 130 fl; MCHC 33 g/dL; RDW, 22%; RBC count, 2.2 million/uL; WBC count, 2600/uL; and platelet count, 95,000/uL. The blood smear was consistent with a maturation defect.

Because of the macrocytosis, a reticulocyte count was ordered, the result was 3%. The above findings point to a diagnosis of _______________ and can be either primary or secondary . What test(s) can be ordered to help determine the cause of the patient’s condition. What are the possibilities that the above test(s) ultimately confirm

myelodysplastic  disease

After an abnormality was detected on a 53-year-old woman’s mammogram, aspiration revealed carcinoma and surgery was scheduled. The patient’s hematologic indices were: hemoglobin level, 10.8 g/dL; MCV, 86 fl; MCHC 33 g/dL; RDW, 12.8%; RBC count, 3.7 million/uL; WBC count, 6800/uL; and platelet count, 250,000/uL.

The anemia in the above case points to what type what condition? To clarify this co-morbid condition what test(s) would you order and what would be their results if the above co-morbid condition is true for this patient?

Dx: anemia of chronic Disease .  Tests ordered would be serum ferritin and serum transfrrin receptor level.

Causes of microcytic anemia may include all of the following except

1. Lead poisoning
2. Thalassemia
3. Iron deficiency
4. Anemia of chronic disease
5. Sickle cell anemia

The chemistry profile of newly admitted patient with anemia reveals a total bilirubin of 2.6 with an elevated LDH. Potential causes of the anemia and hyperbilirubinemia may include all of the following except

1. Malaria
2. Drug use
3. Folate deficiency
4. Blood transfusions
5. Disseminated intravascular coagulopathy

1. Folate deficiency

Causes of hemolytic anemia include all of the following except

1. Blood transfusion reaction
2. Lead poisoning
3. Thrombotic thrombocytopenic purpura
4. Sickle cell anemia
5. Disseminated intravascular coagulopathy

Which of the following is true of idiopathic thrombocytopenic purpura (ITP)?

1. ITP is typically chronic in onset
2. ITP is commonly precipitated by severe bleeding
3. The primary treatment involves transfusion of platelets until bleeding is controlled
4. ITP may be associated with lupus
5. ITP rarely occurs in children

1. ITP may be associated with lupus

Match the appropriate tumor marker with each malignancy

1. PSA              a. Hepatocellular
2. CEA               b. Prostate
3. CA 125          c. Carcinoid
4. AFP                d. Colon
5. Beta-hCG    e. Testicular                                         f. Ovarian

A 56-year-old male comes to your office with the only complaint of feeling quite fatigued. On PE, he appears pale. His BP is 100/80 mm Hg. His pulse is 96 bpm and regular. No other abnormalities are found. A CBC reveals a hemoglobin level of 10 g/dL. His blood smear also shows a decreased MCHC and a decreased MCV

Until proven otherwise, what is the most likely cause of his low hemoglobin level and why?

1. Lymphoma
2. Gastrointestinal malignancy
3. Lack of intrinsic factor
4. Dietary deficiency of folic acid
5. Dietary deficiency of iron

1. Gastrointestinal malignancy

A 78-year-old female comes to your office complaining of a “lack of energy” that began 8 months ago. On exam, the patient has marked pallor. Her hemoglobin level is 7.5 g/dL. A peripheral blood smear reveals hypochromasia  and microcytosis. Her hemoglobin was 13 g/dL 1 year ago.

What is the most likely cause of the patient’s anemia and why?

1. Malnutrition
2. Pernicious anemia
3. Folic acid deficiency
4. Gastrointestinal bleeding
5. hypothyroidism

1. Gastrointestinal bleeding