Pathology of RBC and Bleeding Disorders Flashcards
Hematocrit?
Percentage of whole blood voume occupied by RBC’s
MCV equation?
MCV= HCT/RBC
MCH?
MCH=Hgb/RBC
MCHC?
MCHC=Hgb/Hct
Describe the values for acute blood loss.
- Normal MCV and MCH
- Retic count will be low initially and will slowly rise to compensate for anemia in 6-7 days
- Annemia will show through low Hgb and Hct after 6 to 12 hrs
What anemias are in the catergory of Hemolytic?
- HS
- G6PD def
- SC
- Thalassemia
- PNH
- Immunohemolytic anemia
- Hemolytic anemia due to trauma
What is HS? How to treat? How does it present?
- unstable membrane skeletal proteins on RBC’s
- travel through the spleen where they are destroyed due to their lack of flexibility
- Hypersplenism
- Remove the spleen to increase the lifespan of the RBC’s
- Howell Jolly bodies present with spleen removed
- Anemia, Jaundice, Splenomegaly
Where is G6PD deficiency common?
- Sub sarahan africa
- Middle east
- Mediterranean
What happens in G6PD deficiency?
- Episodic hemolysis due to oxidative stress caused by:
- drugs
- stress
- infection
- fava beans
What are heinz bodies?
- precipitation of denatured Hbg and other stromal proteins due to oxidative damage
- Cells with heinz bodies can’t go through spleen and either get destroyed or heinz bodies removed leading to Bite Cells
What mutation causes Sickle cell?
- Mutation in B chain of Hbg
- GAG to GTG (Glu to Val)
What makes polymerization of Sickle Cell more likely?
- Hypoxia
- Intracell dehydradation
- Low pH
- Sluggish blood flow
- Sickled cells undergo vascular hemolysis
- Vaso occlusion leads to under perfusion looping back around to hypoxia
In what disease will you see target cells?
- SC disease, a milder disease than Sickle Cell
- The Hbg C can crystalize but it doesn’t polymerize
What drug is used to treat sickle cell?
Hyrdoxyurea, it increases HgbF
B Thal Major?
- Severe anemia
- Preferential switch to Hgb F
- Dramatic medullary and extramedullary hematopoiesis
- See “crew cut” from bonw marrow expansion on x ray
What disease is indicated
B Thal Major
B Thal Minor?
- Microcytic anemia
- Mild and asymptomatic
a-Thalassemia 3 genes?
- HbH disease
- High oxygen affinity
- Hemolytic and Microcytic anemia and splenomegaly
a-Thalassemia 4 genes?
Hb Barts (Hydrops Fetalis)
Parozysmal Nocturnal Hemoglobinuria?
- PIGA mutations affecting HSC so all derived cells are affected
- Cells lack CD55 and CD59 to protect them from lysis by complement
What is PNH a risk factor for?
MDS/AML
How do you treat PNH?
- Eculizamab, a targeted therapy that blocks C5 and C5a
What is a “Warm Ab”?
- IgG
- Idiopathic: autoimmune hemolytic anemia
- Secondary:
- CLL
- Lymphoma
- SLE
- Drug related
Cold Ab?
- Idiopathic: Chronic hemagglutinin disease
- Secondary:
- Mono
- Mycoplasma pneumonia
- Lymphoma
What is a direct Coombs test?
- Detects presence of Ab bound to red cell surface
What is the indirect Coombs test?
Detects Ab in the plasma
Warm Hemolytic anemia?
- IgG
- Opsonized cells are phagocytosed in the spleen or they gradually lose their membranes
- Autoimmune or drugs
Cold hemolytic anemia?
- IgM
- Strong affinity at lower temp
- More likely to manifest in the nose and fingertips (raynaud)
- IgM leads to C3b deposition and the liver spleen and bone marrow remove the cells
what is indicated if you have a high retic count? (general)
- Bleeding or destruction of RBC’s
What is indicatetd if you have a low retic count?
- RBC production problem
What causes megaloblastic anemia?
- Impaired DNA synthesis
- Anemia occurs as a result of not being able to produce RBC’s and growth factor production increases
- Marrow hyperplasia occurs but hematopoiesis is ineffective
With megaloblastic anemia what is seen in the peripheral blood?
- Hypoproliferative (low retic)
- Macrocytic (high MCV)
- Ovalocytes
- Neutrophil hypersegmentation
What is pernicious anemia?
- Megaloblastic anemia caused by autoimmunity typically seen in older adults
- Abs directed against parietal cells which secrete Intrinsic Factor
- IF needed for B12 absorption
- B12 needed for DNA synthesis
- Chronic atrophic gastritis can lead to megaloblastic anemia
- which can lead to spinal (and brain/peripiheral nerves) demyelination
What byproduct of DNA synthesis is high in Pernicious anemia?
- High levels of homocysteine/ MM Co-A
Iron Deficiency Anemia
- hypoproliferative
- Microcytic
- Hypochromic
- Anisocytosis
Physical manifestations of Iron deficiency anemia?
- Koilonychia
- Alopecia
- Atrophic glossitis
- [Angular chelitis
With IDA what will iron studies show?
- Low serum iron
- Low serum ferritin
- Low Hepcidein
- Increased TIBC
What is Anemia of chronic disease?
- Impaired RBC production/iron utilization in chronic illnesses
- Chronic illness makes the body horde iron instead of utilizing it
- Looks similar to IDA
What will an Iron study show with Anemia of chronic disease?
- Low serum iron
- Reduced TIBC
- Increased ferritin
- Abundant iron in the tissues
A: normal bone marrow
B: Aplastic Anemia
How do you diagnose Aplastic anemia?
- Anemia
- Thrombocytopenia
- Leukopenia
- Bone marrow full of adipose
when do you see pure red cell aplasia?
- Very rare, seen with thymomas
- Parvovirus B19 when there is hemolytic anemia
- The BM shows decreased erythroid precursors
What is Myelophthisic anemia?
- Space occupation in the bone marrow seen in metastatic cancer, fibrosis,inflammation, and necrosis replacing the normal hematopoietic cells
- Abnormal release of erythroid and granulocyte precursors results in leukoerythroblastosis (pic)
Periorbital bruising can be a sign of what cancer?
Myeloma with perivasscular amyloid deposition
What will a patient with Immune thrombocytopenic purpura present with? How do you treat?
- Petechiae and purpura
- CBC shows thrombocytopenia, and potentially Ab’s to platelets
- BM shows increased megakaryocytes due to the lack of platelets
- Tx by reducing the immune response with corticosteroids, IVIg, and Rituximab (anti-CD20)
What is the pentad of Thrombotic thrombocytopenic purpura?
- Fever
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Neuro defects
- Renal failure
What causes TTP? How to treat?
- ADAMTS13 is defective, this is the metalloproteinase that breaks down the multimers of vWF and without this we get massive sized platelet aggregations
- Plasma exchange therapy
What is the typical presesntation of Hemolytic Uremic Syndrome? and atypical?
- Shiga like toxin elaborated by E. coli O157:H7 (bloody diarrhea)
- atypical is variable linked to complement dysfunction
- Tx is supportive
What is Bernard Soulier and Glanzmann thrombasthenia?
- BS: no adhesion occurs
- GT: no aggregation occurs
vWF disease type 2 and 2A?
- 2: qualitative defects defined by lack of appropriate interaction with ligands
- 2A is most common and defined by a lack of multimer assembly
Who is the universal red cell donor and recipient?
- Donor is O
- Recipient is AB
Who is the universal Plasma donor and recipient?
- Donor: AB
- Recipient: O
What is a TRALI?
- Acute respiratory failure during or after a transfusion with diffuse bilateral pulmonary infiltrates
- May have fever or hypotension and can be fatal
