Heme Disease: quick facts

Range of Hgb

males 14-18

females 12-16

Range of Hct

males 42-52%

females 37-47%

Range of MCV

80-100

Range of MCH

30-34

Range of MCHC

31-37

Range of WBC

5-10 K/uL

Range of platelets

150,000-450,000 uL

MCV <80

LITS= lead poisoning, iron deficiency, thalassemia, sideroblastic (for this class, cram Pance is different)

Microcytic Anemia

• most common cause of anemia

• blood loss is most common cause

• microcytic, hypochromic

• Patho: low iron = low RBC production

• Labs: dec MCV, MCH, low iron, low ferritin, high transferrin, low TIBC saturation

• Tx: iron supplementation

Iron Deficiency Anemia

• Patho: abn globin → hemolysis

• Mediterranean, Africa, Asia (where malaria is)

• Smear: stippled, target, elliptical cells

• Labs: low MCV, low MCH, normal iron studies

• Dx: use Hgb Electrophoresis (inc HbA2, HbF, HbH)

• Tx: minor= no tx; major: transfusion, iron chelating, folate supplementation, splenectomy

Thalassemia (general)

• 4 genes

  • 1 deletion: asymptomatic

  • 2 deletions: mild anemia

  • 3 deletions: severe anemia (transfusion dependent)

  • 4 deletions: hydrops fetalis (die)

Alpha- Thalassemia

• more common

• 2 genes

  • 1-Beta Thalassemia Minor: mild anemia, asymptomatic

  • 2-Beta Thalassemia Major: severe anemia, frontal bossing, hair on end skull X-ray, extra medullary hematopoesis

Beta-Thalassemia

• microcytic, hypochromic

• basophilic stippling

• vague sx

• Labs: above 10 mcg/dl is toxic

• Tx: chelation, supportive care

Lead Poisoning Anemia

• accelerated destruction

  • extravascular (damage, immune response)

  • intravascular (TTP, G6PD, Thalassemia, hereditary spherocytosis)

• Labs: inc Bilirubin, inc LDH, dec Haptoglobin, high inc in reticulocytes

Hemolytic Anemia

• MCV 80-100

• analyze reticulocyte count → problem

  • elevated: blood loss, AIHA, G6PD

  • normal/low: chronic disease, CKD, BMF, myelofibrosis

Normocytic anemia

• Chronic

  • microcytic, small bleeds, slow development

• Acute

  • large volume loss, quick onset, high inc in reticulocytes, normocytic

Anemia of Blood Loss

• most common RBC enzyme defect

• X-linked recessive = males

• sx under oxidative stress

  • stress → hemolysis

  • infection = most common stressor

• Labs: normal MCV

• Smear: Heinz bodies, bite cells

• Tx: supportive, tx underlying cause, acute: transfusion

“stress makes me eat bites of fries w/ Heinz ketchup”

G6PD Deficiency

• antibodies and complement destroy RBCs

• Warm: IgG, most common

• Cold: IgM

I’m always cold

Autoimmune Hemolytic Anemia (AIHA) -general

• idiopathic, 2^o to malignancy, virus, drugs, immunodeficiency

• asymptomatic, anemia, jaundice, splenomegaly

• Labs: inc LDH, inc reticulocytes, inc bilirubin, low hapto

• Coombs (DAT)= +

• Anti-C3= +

• Tx: corticosteroids, folic acid

Warm AIHA

• Chronic: older, more common

• Acute: rare, self-limiting

• Labs: inc LDH, inc reticulocytes, inc bilirubin, low hapto

• RBC agglutination

• DAT= + for C3 only

• Cold agglutination = +

• Tx: supportive measures

Cold AIHA

• most common cause of normocytic anemia

• malignancy, RA, CKD, IBD, DM

• results from dec RBC production

• Labs: dec reticulocyte count, low iron, high ferritin, low TIBC

• Tx: underlying cause, Severe, EPO supplementation

Anemia of Chronic Disease

• results from low EPO

• Smear: burr cells

• Labs: normal ferritin, low EPO, low iron, low transferrin

• Tx: EPO injections

Anemia of CKD

• inadequate blood cell production → low RBC, potentially low WBCs and plts

• acquired or congenital

  • Ex: aplastic anemia

Bone Marrow Failure Syndromes

• pancytopenia: anemia, thrombocytopenia, neutropenia

• autoimmune attack on stem cells

• dec plt production

• Dx: bone marrow biopsy

• Tx: refer to hemat, transfusions, immunosuppression

Aplastic anemia

• colonial disorder: fibrotic tissue replaces bone marrow

  • extra medullary hematopoiesis

• Pancytopenia

• Tx: JAK2 inhibition, stem cell transplant

Myelofibrosis

• MCV >100

• Megaloblastic - hypersegmented neutrophils

  • B12 deficiency

  • Folate deficinecy

• Non megaloblastic -no hypersegmentation

  • MDS

Macrocytic Anemia

• folate deficiency is the most common cause

• B12 is less common

• Dx: macrocytosis, hypersegment neutrophils, Howell-Jolly

• shilling’s test = checks b12 uptake

Megaloblastic Anemia

• __ is needed for the formation of normal RBCs

• animal products

  • can take yrs to deplete stores (chronic)

• pernicious anemia is a common cause

  • PA= lack of intrinsic factor

• Sx: neurological signs

• Dx: inc MCV, inc homocysteine, inc MMA

• Tx: ___ PO or IM

B12 deficiency

• __ cofactor in DNA synthesis

• 2-3 month supply

• leafy greens

• due to inadequate intake

  • deficit in alcoholics, pregnancy

• Labs: high MCV, low folic acid, inc homocysteine, MMA normal

• Tx: oral supplements

Folate Deficiency

• ineffective hematopoesis

• pancytopenia w/ macrocytic anemia

• low reticulocytes

• → AML

• bone biopsy needed

• Tx: growth factors, stem cell transplant

Myelodysplastic Syndrome

• defect in Hgb

  • quantitative = Thalassemia

  • qualitative= Sickle Cell

  • defect in synthesis of heme= porphyias

Hemoglobinopathies

• autosomal recessive; African Americans more common

• defect on chromosome 11 → mutation of beta chain: HgB → HgS

  • SS, SC, Sickle-B thalassemia

  • HgS→ less soluble

• can cause hemolytic anemia

• Dx: Hgb Electrophoresis

• Labs: dec H&H, inc WBCs, sickle cells, target cells, Howell-Jolly

• pain crisis, acute chest syndrome

• Tx: ER= transfusion or correct pain crisis event

  • Hydroxurea, stem cell transplant

Sickle Cell Disease

• acquired, EPO disorder (MDS)

• accumulation of iron → ringed sideroblasts

• Labs: low MCV, inc iron, inc ferritin, low TIBC

• Tx: transfusion, avoid offending toxin, bone marrow transplant

Sideroblastic Anemia

• altered activity of 1/8 enzymes involved in heme biosynthesis

• RARE

• no cure

• severe photosensitivity (avoid sun)

• 3 types: acute, blistering, non-blistering

  • Tx acute with Hemin

Porphyrias

• most common in adults

• changes of sun-exposed skin

• blistering

• measure plasma or urine porphyrins

Porphyria Cutanea Tarda (PCT)

• 2nd most common

• pain, nausea, weakness

• psych changes

• measure porphobilinogen

• Tx: Hemin

Acute Intermittent Porphyria (AIP)

• most common in children

• pain to sun-exposed skin w/in minutes

• erythema, swelling

• no blistering

• measure erythrocyte total protoporphyrin

Erythropoietic porphyria (EPP)

• donor cells see host a foreign → attack

• common: skin, gut, liver

• HLA most important thing to match

• prevention is key

• Tx: immunosuppressives

  • steroids

Graft vs Host Disease (GVHD)

• adhere

• activate

• aggregate → platelet plug

Primary hemostasis

• coagulation cascade activated

  • fibrinogen → fibrin

Secondary hemostasis

• cross linking of fibrin

• clot maturation

• wound healing

Tertiary hemostasis

• inc plt destruction, acquired

• autoimmune, females > males

  • antibodies against plts

• no apparent cause

• mucocutaneous bleeding

• acute seen in kids, chronic adults

• Dx: exclusion

• Labs: thrombocytopenia, PT/PTT normal, neg D-dimer, no schistocytes

• Tx: IVIG, glucocorticoids (steroids), splenectomy

Immune Thrombocytic Purpura (ITP)

• life-threatening

• autoantibodies cross-react with plts

• Heparin exposure

• activated plts → hyper coagulable (both venous and arterial thrombosis)

• Dx: sudden thrombocytopenia, HIT antibody +, PT/PTT normal

• Tx: stop heparin, start non-hep anticoagulant (direct thrombin inhibitor) (argatroban), avoid plts

Heparin-Induced Thrombocytopenia (HIT)

• inc von Willebrand Factor

• fever, anemia (MAHA), thrombocytopenia, renal failure, neurologic changes

• ADAMTS13 deficiency

• factors falsely trigger platelet plug formation w/o injury

• ischemia, organ failure, death

• Labs: PT/PTT N, D-dimer negative, schistocytes

• Tx: plasma exchange, glucocorticoids, Rituxan, caplacizumab

Thrombotic Thrombocytopenia Purpura (TTP)

• heterogeneous group of disorders characterized by proliferation of 1+ cell line in the peripheral blood

• Ex: polycythemia vera, essential thrombocythemia, CML

myeloproliferative neoplasm

• clonal disorder w/ proliferation and maturation of erythoid, megakaryocytic, and granulocytic elements

  • Hb >16.5 F, > 18.5 M

• Labs: inc H&H, potential inc WBC & plt, low EPO, JAK2 mutation

  • inc EPO → secondary

• Sx due to poor oxygenation of tissues due to blood hyperviscosity

• Tx: stem cell transplant, prevent event, ASA daily, therapeutic phlebotomy (removal of 400-500mL blood 1-2 x weekly until Oct <45%)

Polycythemia Vera

• Labs: JAK2 mutation, high plts

• Risks:

  • high: hx of thrombosis, >60 you w/ JAK2

  • intermediate: >60 yo, no JAK2, no hx thrombosis

  • low: <60yo, JAK2, no hx of thrombosis

  • very low: <60 yo, no JAK2, no hx of thrombosis

• Sx: vasomotor, hemorrhagic, thrombotic, splenomegaly

• Tx: ASA daily, hydroxyurea, tx underlying cause

Essential thrombocythemia

• abn accumulation of iron → organ toxicity

• most common inherited liver disease

• most common cause of severe iron overload

  • heart, liver, pancreas, pituitary gland, joints, skin

• men > women; Northern European origin

• apparent later in life; women even later due to menses

• “bronze diabetes” → skin pigmentation

• HFE1 gene on chromosome 6; genetic testing

• Sx: asymptomatic, low libido, darkening of skin

  • cirrhosis, abn liver function, liver cancer

• Tx: lower iron: phlebotomy, chelation, avoid excessive intake

Hemochromatosis

Transfusions

• obtain written consent

• only given after careful evaluation

Whole Blood

• whole blood minus plts

• use has been replaced by PRBC infusions

• used for large volume blood loss

RBC components

• PRBCs

• leukodepleted RBCs

• Washed RBCs

• frozen RBCs

• irradiated red cells

• CMV- cells

RBC transfusion

• share of risk

• used to improve O2 delivery, not treat hypovolemia

• inc Hgb by 1

Platelets

• treat thrombocytopenia

• prevent bleeding

• ex: pooled random donor plts

  • single donor pheresis plts

  • HLA-matched single donor plts

Coagulation Factors

• FFP

  • massive blood loss

  • ER reversal of warfarin

  • DIC

• Cryoprecipitate

  • Factor 8 deficiency

  • fibrinogen replacement

  • DIC

• Purified and recombinant factor preps

  • inherited factor deficiencies

Transfusion Complications

• hemolytic reactions

• febrile reactions

• allergic reactions

• infectious agent transmission

Transfusion Reaction Hemolysis

• fever, chills, chest pain, hypotension

• imending doom

• STOP transfusions immediately

• Transfusion of mismatched blood can be FATAL

• x-linked recessive = males

• most common Hemophilia

• deficiency in Factor 8, intrinsic pathway

• hemarthrosis

• Labs: PT, PTT inc, Factor 8 assay low

• Tx: Factor 8 infusions, DDAVP (only for this one)

Hemophilia A

• Christmas disease; Factor 9 deficiency

• x-linked = males, Jews, milder

• hemarthrosis

• Labs: PT N, prolonged PTT, factor 9 assay low

• Tx: factor 9 infusion, antifibrionolytics

Hemophilia B

• Labs: inc PT/PTT, inc liver enzymes, dec Vit K, factors 2, 7, 9, 10

• Tx: underlying disorder, parenteral infusion, FFP for hemorrhage

Vit K deficiency

• most common inherited bleeding disorder

• autosomal dominant M=F

• mucocutaneous bleeding

• Labs: assays, RIPA, PT N, inc PTT, vWF antibody low

• Tx: DDAVP (T1), vWF concentrates (T2 & 3)

von Willebrand Deficiency

• ongoing coagulation and fibrinolysis

• production of thrombi, blood oozing form wounds

• very sick pts

• Labs: thrombocytopenia, inc D-dimer, inc PT/PTT, low fibrinogen, schistocytes, dec Protein C

• Tx: supportive, cryoprecipitate for low fibrinogen, anticoagulation if hypercoagulative, wait

Desseminated Intravascular Coagulation (DIC)

• preeclampltic, eclamtic

• intravascular hemolysis

• elevated liver enzymes

• low plt count

• third trimester, epigastric/RUQ pain, nausea/vomiting

HELLP Syndrome

• much less neurologic sx, more likely renal failure

• E. coli 0157:57

• bloody diarrhea, renal failure

• thrombocytopenia, MAHA, AKI

• Labs: Serum Cr inc significantly

• Tx: supportive, hemodialysis

• inc mortality in older children and adults

Hemolytic Uremic Syndrome (HUS)

• most common VTE

• 5x more deaths than breast cancer

• unilateral

DVT

• SOB

• tachypneic

• chest pain

• hemoptysis

PE

• Vit K dependent, autosomal inherited

• homozygous → neonatal purpura, DIC

• hypercoagulabe state

• VTE, warfarin induced necrosis

• Labs: protein assay

• Tx: anticoagulation

Protein C & S Deficiency

• most common inheritable clotting disorder

• hypercoagulable state

• VTE, miscarriages

• Labs: genetic testing, Protein C resistance assay

• Tx: anti coagulation

Factor V Leiden