hemo julia Flashcards
Anemia =
RBC, Hematocrit and Hemoglobin decrease
Present with pallor, fatigue, weakness, dyspnea, palpitations, heart failure – any or all symptoms
How does anemia occur?
Acute blood loss (trauma)
Chronic blood loss
- Usually from GI tract – such as bleeding ulcers or carcinoma, etc.
- From Gyn – increased menses, postmenopausal bleeding, etc.
Increased destruction of RBCs = hemolytic anemias
Decreased or impaired production
Impaired production of RBCs by…
problem in proliferation of stem cells (e.g., aplastic anemia)
problems of proliferation and maturation of erythroblasts
defective DNA synthesis (e.g. Megaloblastic anemia)
defective heme synthesis (e.g Iron deficiency anemia)
defective globin synthesis (e.g. thalassemia)
Hemolysis: intra vs extravascular
= broken down/burst RBC
Intravascular hemolysis (in vessels)
- Common causes include mechanical trauma (e.g., prosthetic heart valves), PNH, and severe G-6-PD deficiency.
-Characterized by hemoglobinemia, hemoglobinuria, and decreased serum haptoglobin
- no splenomegaly
Extravascular hemolysis (spleen)
- presentation = anemia, splenomegaly, jaundice
- cause: Changes that make red cells less deformable, leading to their premature destruction in the spleen
- ex: Hereditary spherocytosis, Autoimmune hemolytic anemia, Thalassemia, Sickle cell disease
Hereditary causes of hemolysis
RBC membrane problems (hereditary spherocytosis)
- Defects in membrane proteins like ankyrin and spectrin cause RBCs to lose their biconcave shape, becoming spherical without normal central pallor. (very fragile and breakdown easily)
- hemolysis as they pass through the spleen
Enzyme disorders (e.g., G-6-PD deficiency)
-reduces RBCs ability to protect themselves against oxidative injuries
- Episodic hemolysis caused by exposures that generate oxidant stress
- triggers: ingestion of oxidant drugs (chloroquine), fava beans, or infections.
Hgb disorders:
- sickle cell anemia
- Thalassemia (alpha and beta)
Acquired causes of hemolysis
RBC membrane problem (paroxysmal nocturnal hemoglobinuria)
- Acquired mutation in the PIGA gene = RBCs more susceptible to complement-mediated lysis
Antibody mediated: antibodies and/or complement binding to the surface of RBCs and destroying our RBcs
- warm antibody
- cold agglutinin ds
- cold hemolysin
Mechanical trauma (e.g prosthetic heart valves)
Others include infections, drugs, toxins, splenic sequestration
Hemolytic anemia, General labs
Life span of the RBC is less than the normal of 120 days.
There is usually bone marrow erythroid hyperplasia = compensating response to…
- loss of RBC
- release of erythropoietin (EPO) produced by kidney
Lab findings:
- Decreased RBC lifespan.
- Increased bilirubin
- Hemosiderosis.
- Reticulocytosis (elevated reticulocyte count) that indicates active RBC production
- breakdown of RBCs releases heme, which is converted into unconjugated bilirubin
- Excess iron from hemolysis is stored as hemosiderin in tissue
Coombs tests
Coombs tests = always used in work-up of hemolytic anemias
- helpful in diagnosing autoimmune hemolytic anemia
Direct – rbc cells tested for surface antibodies
Indirect – serum tested for antibodies
Hereditary Spherocytosis
= Autosomal dominant genetic defect affecting RBC membrane proteins such as Ankyrin and spectrin
RBCs will be round without normal central pallor
==> These spherocytes are fragile and break down.
G-6-PD deficiency
G-6-PD = an enzyme which converts glucose-6-phosphatase
- Rate limiting step of pentose phosphate pathway
- Genetics: X-linked or recessive.
==> Hemolysis may occur after eating some types of food (classically Fava beans) or use of oxidant drugs ( chloroquine or infections)
- enzyme deficiency reduces RBCs ability to protect themselves against oxidative injuries. Episodic hemolysis caused by exposures that generate oxidant stress
Usually either recessive or X-linked
Morphologically RBCs will show HEINZ bodies which is precipitated/denatured hemoglobin
Sickle cell anemia
= Hemoglobinopathy
- Heterozygous versions are usually asymptomatic; need HOMOZYGOTES
- Protection against Malaria
Recall normal globin chains are alpha2 beta 2 ~~~~~> Sickle cell anemia is a BETA chain defect (amino acid substitution)
- cells become stiff and sticky under hypoxic conditions
There may be jaundice, pain, vaso-occlusive disorders (sickle cells get “stuck” in vessels).
There is also susceptibility to infections such as Strep. pneumonia or Salmonella osteomyelitis
Sickle cells trapped in sinusoids –> Spleen can basically become non-functional (auto infarct) –> infections with encapsulated microorganisms are more prevalent since the spleen is important in dealing with these types of microorganisms.
- Vaso-occlusive crises (painful episodes) -> Sickled cells can’t move smoothly through small blood vessels, so they can get stuck and block blood flow
- MICROVASCULAR OBSTRUCTION
- ISCHEMIC TISSUE DAMAGE
- Susceptibility to ENCAPSULATED bacterial infections due to splenic dysfunction… Sickle cells can get trapped in the spleen, damaging it. The spleen is an important organ for fighting infections, especially encapsulated organisms
- Streptococcus pneumoniae
- Salmonella osteomyelitis
Thalassemia
Hgb Alpha or Beta chain problems, aka deficient synthesis
- Inherited deficiency
Morphology: “Crew cut” skull X-ray because of erythroid hyperplasia expanding bone
Alpha:
- one missing gene: no sx
- four missing genes: hydrops fetalis - usually fatal (fetus does not make it to term) … If born, infant will have severe hemolytic anemia, edema (hydrops), massive hepatosplenomegaly
beta: varying degrees of severity
- one: mild anemia
- two: severe anemia
paroxysmal nocturnal hemoglobinuria
= Acquired mutation of PIGA (gene for enzyme needed to make certain RBC membrane complement regulatory proteins) = acquired RBC membrane disorder
- RBCs more susceptible to complement-mediated lysis
Not always paroxysmal or nocturnal
Don’t need to know too much about this
Immunohemolytic Anemias
Immunohemolytic Anemias = antibodies and/or complement present on RBC surface
= autoantibodies that react with red blood cells at temperatures ≥ 37° C (warm antibody hemolytic anemia) or < 37° C (cold agglutinin disease)
- May not be auto-immune, can be causes by certain drugs
warm IgG (will not hemolyze at room temperature)
- may be idiopathic or secondary to malignancies (i.e. lymphomas and leukemias)
cold agglutinin IgM (will hemolyze at room temperature)
- Mycoplasma pneumoniae, HIV, mononucleosis
cold hemolysin IgG
- e.g. cold paroxysmal hemoglobinuria (very rare subtype of autoimmune hemolytic anemia, caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria
- typically after exposure to cold temperatures
Hemolytic Anemias due to Trauma overview
-Mechanical Heart Valves:
Microangiopathies:
- Thrombotic Thrombocytopenic Purpura (TTP): pentad - of fever, thrombocytopenia, anemia, renal and neurological manifestations, deficiency of enzyme ADAMTS-13
- Hemolytic Uremic Syndrome (HUS): usually follows E. coli GI infections in children + acute kidney injury!!!!
Anemias due to decreased/impaired production include:
- Megaloblastic anemia: impaired DNA synthesis, due to low B12 or folate
- Iron deficiency
- Anemia of chronic ds
- aplastic anemia
Megaloblastic Anemia: define and causes
Definition: Anemia caused by impaired DNA synthesis, which results in large RBCs (macrocytic anemia) and hypersegmented neutrophils (neutrophils with ≥4 lobes).
Vitamin B12 Deficiency: need for DNA synthesis
- decreased dietary intake
- lack of intrinsic factor (as seen in pernicious anemia)
- malabsorption in the terminal ileum
- sx: neurological *** - numb + tingling
Folate Deficiency:
- poor diet
- alcoholism
- intestinal malabsorption
- increased demand (e.g., pregnancy, infancy)
- drugs (e.g., anticonvulsants, chemotherapy)
- hemodialysis: increased loss
- NO NEUROLOGICAL SX
Iron Deficiency Anemia: definition, lab, causes
Anemia due to insufficient iron, which is needed for hemoglobin synthesis
- RBCs are microcytic and hypochromic (small and paler)
Labs:
- Decreased serum iron levels are decreased, transferrin saturation, and ferritin
- Increased Total iron-binding capacity (TIBC): measures the blood’s capacity to bind iron with transferrin
causes:
- Increased Iron Loss: Often due to bleeding (GI bleed, heavy menstrual periods).
- Decreased dietary Iron Intake
- Malabsorption: celiac disease
Ferritin and transferrin define
Ferritin
- protein for iron storage, releases iron as body requires
- Low levels indicate low iron storage
- Stored in the body’s cells until it receives body’s signal to make more red blood cells
- ferritin then binds to transferrin.
Transferrin:
- protein that combines with ferritin to transport it to where new red blood cells are made
Anemia of Chronic Disease
chronic infections, chronic immune diseases, neoplasms, liver or kidney failure
Very similar to iron deficiency anemia
- Iron is present in the bone marrow in anemia of chronic disease unlike in iron deficiency anemia**
- iron stores/hemosiderin are normal or increased (elevated ferritin) but not properly utilized
- microcytic and hypochromic
Aplastic anemia
All 3 cell lines (RBCs, WBCs, and platelets) are affected
Can be idiopathic, caused by drugs, radiation, or viruses
Fanconi’s anemia = a disorder of aplastic anemia which is also associated with
- short stature, skeletal abnormalities, and increased risk of solid tumors and leukemias
Primary (Polycythemia Vera) vs Secondary Polycythemia
Polycythemia = increased RBCs, hemoglobin, hematocrit
- category: Primary (Polycythemia Vera) vs Secondary Polycythemia
Primary: polycythemia vera - caused by genetic mutation bone marrow
- Myeloproliferative disease: disorder where the bone marrow makes too many rbcs, wbcs, and platelets.
- EPO = LOW
Secondary: body makes more RBCs due to high erythropoietin (EPO) levels
- EPO = HIGH
- kidney tumor, high altitude, EPO doping for athletes
Bleeding Disorders categories
Blood Vessel Wall Abnormalities
Platelet Quantity (Thrombocytopenia)
Platelet Function (Quality)
Abnormal Clotting Factors
Disseminated Intravascular Coagulation (DIC)
bleeding ds: Blood Vessel Wall Abnormalities: types
Infections:
- Meningococcemia
- Rocky Mountain Spotted Fever can damage vessel walls
Drugs: Some medications can weaken vessel walls.
Collagen Defects:
- scurvy (vitamin C deficiency) lead to poor collagen production, weakening blood vessels.
- henoch-schönlein purpura (deposition of immune complexes within vessel wall and kidneys)
Hereditary Hemorrhagic Telangiectasia
- Weber-Osler-Rendu Syndrome: An inherited disorder where blood vessels are dilated but fragile, causing easy bleeding.
bleeding ds: Decreased Platelet Numbers (Thrombocytopenia) categories
splenic sequestration, dilutional effect (multiple transfusions)
decreased production (in aplastic anemia, alcoholism, some chemotherapy, etc.)
decreased survival and increased platelet destruction (Immune Thrombocytopenic Purpura , Thrombotic Thrombocytopenic Purpura, Hemolytic Uremic Syndrome, DIC, drugs, infectious diseases (e.g. HIV))
Immune thrombocytopenic purpura (ITP): acute vs chronic and considerations
Acute ITP : autoimmune
- usually occurs in children after a viral illness who develop anti-platelet antibodies
- usually self-limited
Chronic ITP
- occurs in adults
- diagnosis of exclusion
- Has decrease in platelet numbers but normal PT/PTT (measures clotting factors)
- large platelets in the circulation
- autoimmune: anti-platelet antibodies, increase in bone marrow megakaryocytes (compensatory mechanism)
- Usually treated with steroids and sometimes splenectomy
Never give a patient with ITP a platelet transfusion !!!!!!
- autoantibodies will destroy the platelets entered into the circulation by the transfusion
Thrombotic Thrombocytopenic Purpura (TTP) : def, what is the pentad
serious blood disorder characterized by the formation of blood clots in small vessels (microthrombi)
Pentad presentation
- Microangiopathic anemia : Characteristic schistocytes (helmet cells) -> As RBCs travel through microthrombi they become sheared or fragmented
- Thrombocytopenia
- Fever
- Neurological manifestations **
- Renal manifestations (neurological more so than renal)
Thrombotic Thrombocytopenic Purpura (TTP) : cause and tx
Causes:
- acquired: antibodies
- inherited: deficiency of the ADAMTS-13 enzyme: breaks down large multimers of von Willebrand Factor (vWF) -> large vWF multimers remains and can aggregate -> platelet activation -> thrombi -< CONSUMPTIVE COAGULOPATHY
Tx: plasma exchange to remove antibodies
Hemolytic Uremic Syndrome (HUS):
similar to TTP but renal manifestations (e.g. increase in BUN/Cr) are more likely than neurological
- Usually follows a GI E. coli infection from eating uncooked meat, etc.
- The E. coli produce a toxin
- endothelial damage and dysregulated platelet activity
SCHIStoCYTES
- sx: thrombocytopenia, and acute kidney injury!!
decreased platelet function (quality): causes
- usually genetic cause
Bernard-Soulier disease = platelet receptor deficiency –> faulty platelet adhesion = BLEED
Glanzmann’s thrombasthenia = different platelet receptor defect –> faulty platelet aggregation = BLEED
Other qualitative platelet disorders include Storage pool diseases
abnormal clotting factors: acquired vs inherited caused
Acquired – Vitamin K deficiency ( Vit K needed for factors II, VII, IX, X)
Inherited – vonWillebrand disease (most common), Hemophilia A, Hemophilia B
- elevated PTT
- normal platelet count and PT
= BLEEDING Disorder
Hemophilia A vs Hemophilia B
Hemophilia A = Factor VIII deficiency, X-linked recessive
- X-linked recessive (more common in males).
- Normal platelets/PT, but prolonged PTT due to intrinsic pathway involvement.
- normal ristocetin test
- tx: recombinant factor VIII
- Deep tissue bleeding (e.g., joints, muscles).
Hemophilia B = “Christmas disease” = Factor IX deficiency
- Inc PTT only, rest is NL
- Factor IX is also in the intrinsic pathway so PTT is increased, but PT is normal
PT = 3 + 7 = 10
PTT: 12, 11, 9, 8
Common: 10/5 = 2 * 1
vonWillebrand disease: overview and lab results
1% prevalence, may be autosomal dominant but autosomal recessive variants occur.
- Inc BLEEDING time, inc PTT, inc PT, normal platelet number
- vWF normally complexes with Factor VIII and bridges underlying collagen of injured vessel to platelets = Therefore Factor VIII is also affected and it is in the INTRINSIC pathway, measured by PTT
No agglutination with Ristocetin Assay since vWF is defective
- Ristocetin is an antibiotic that causes vWF to bind to platelets.
disseminated intravascular coagulation: overview and causes, tx
= pathological activation of coagulation cascade caused by many different things
–> widespread formation of microthrombi –> As the platelets are used up to make the microthrombi, the platelet count decreases
==> Therefore both coagulation factors and platelets are consumed (consumptive coagulopathy)
Possible causes - trauma, obstetrics complications, sepsis, some types of adenocarcinoma, acute promyelocytic leukemia
- Treat underlying cause
acute vs chronic DIC
Acute DIC – usually more associated with bleeding
- more likely caused by OB complications, sepsis, and trauma
Chronic DIC – usually more associated with thrombosis
- more likely caused by malignancy
