RBC disorders (Pathoma Robbins) Flashcards
(91 cards)
1
Q
P: What is the basic principle of anemia?
A
Reduction in circulating RBC mass
2
Q
P: What does anemia present with?
A
Signs and symptoms of hypoxia:
- weakness, fatigue, dyspnea
- pale conjunctiva and skin
- headache and lightheadedness
- Angina, especially with preexisting CAD
3
Q
P: _____, _____, _____ are used as ______ for RBC mass, which is difficult to measure
A
Hb, hematocrit, RBC count;
surrogates
4
Q
P: How is anemia defined in males and females? What are the normal Hb counts in men and women?
A
Men: Hb <12.5 g/dL
Normal men: 13.5-17.5
Normal women: 12.5-16.0
5
Q
P: Based on mean corpuscular volume…
A
anemia can be classified as microcytic (100)
6
Q
P: How is microcytic anemia defined? What is it due to?
A
Anemia with MCV < 80 um3;
due to decreased production of hemoglobin (RBC progenitor cells in the bone marrow are large and normally divide multipe times to produce smaller mature cells (80-100 = MCV), but microcytosis is due to an “extra” division which occurs to maintain Hb concentration)
7
Q
P: Hb is made of…;
A
Heme and globin
8
Q
P: What is heme made of? Decrease in what components leads to microcytic anemia?
A
Protoporphyrin and iron; microcytic anemia
9
Q
P: What do microcytic anemias include?
A
- Iron deficiency anemia
- Anemia of chronic disease
- Sideroblastic anemia
- Thalassemia
10
Q
P: What is iron deficiency anemia due to? It is the most ____ type of anemia
A
Iron goes down, heme then goes down, Hb goes down, hence the microcytic anemia; common (lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of world’s population)
11
Q
P: Iron is consumed in ____ and _____ forms; write out the path of what happens to the iron once consumed
A
heme (meat-derived ) and non-heme (vegetable-derived);
- Absorption occurs in duodenum; enterocytes have heme and non-heme (DMT1) transporters; the heme form is more readily absorbed
- Enterocytes transport iron across the cell membrane into blood via ferroportin
- Transferrin transports iron in the blood and delivers it to liver and bone marrow macrophages for storage
- Stored IC iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction
12
Q
P: List the lab measurements of iron status
A
- Serum iron (measure iron in blood)
- TIBC (measure of transferrin molecules in the blood)
- % saturation (percentage of transferrin molecules that are bound by iron, normal is 33%)
- Serum ferritin (reflects iron stores in macrophages and liver)
13
Q
P: Iron deficiency is usually caused by _____ or _____
A
dietary lack; blood loss;
- infants: breast-feeding (human milk is low in iron)
- Children (poor diet)
- Adults (20-50 years): peptic ulcer disease in males and menorrhagia or pregnancy in females
- Elderly: colon polyps/carcinoma in the Western world; hookworm in the developing world (Ancylostoma and Necator)
- Other causes include malnutrition, malabsorption, and gastrectomy (since acid aids iron absorption by maintaining the Fe2+ state, which is more readily absorbed than Fe3+)
14
Q
P: Stages of iron deficiency:
A
- Storage iron is depleted (decreased ferritin, more TIBC)
- Serum iron delpleted (decreased serum Fe and %sat)
- Normocytic anemia (bone makes fewer but normal-sized RBC’s)
- Microcytic, hypochromic anemia (bone marrow makes smaller AND fewer RBCs)
15
Q
P: Clinical features of iron deficiency include:
A
anemia, koilonychia, pica
16
Q
P: Lab findings of iron deficiency anemia include:
A
- Microcytic, hypochromic RBCs with increased red cell distribution width
- decreased ferritin, increased TIBC, decreased serum iron, decreased % sat
- Increased free erythrocyte protoporphyrin (FEP)
17
Q
P: What does treatment of IDA include?
A
supplemental iron (ferrous sulfate)
18
Q
P: Plummer-Vinson syndrome is
A
iron deficiency anemia with esophageal web and atrophic glossitis, presenting as anemia, dysphagia, beefy-red tongue
19
Q
P: Anemia of chronic disease is associated with
A
chronic inflammation (endocarditis or autoimmune conditions) or cancer; most common type of anemia in hospitalized patients
20
Q
P: Chronic disease anemia results in
A
production of acute phase reactants from the liver, like hepcidin (this sequesters iron in storage sites by limiting iron transfer from macrophages to erythroid precursors and suppressing EPO production, aiming to prevent bacteria from accessing iron)
21
Q
P: What causes anemia of chronic disease?
A
Decreased available iron, decreased heme, decreased Hb, microcytic anemia!!
22
Q
P: Lab findings for anemia of chronic disease include
A
increased ferritin, decreased TIBC, decreased serum iron, decreased % saturation;
Increased free erythrocyte protoporphyrin
23
Q
P: Treatment of anemia of chronic disease includes
A
addressing the underlying cause
24
Q
P: sideroblastic anemia is due to
A
defective protoporphyrin synthesis: decreased protoporphyrin leads to decreased heme, decreased Hb, microcytic anemia
25
P: how is protoporphyrin synthesized?
1. Aminolevulinic acid synthetase converts succinyl CoA to aminolevulinic acid using vit B6 as a cofactor (RATE-LIMITING STEP)
2. Aminolevulinic acid dehydratase converts ALA to porphobilinogen
3. Additional reactions convert porphobilinogen to protoprophyrin
4. Ferrochelatase attaches protoporphyrin to iron to make heme (final reaction: IN MITO)
26
P: In sideroblastic anemia, iron is transferred to ____ ____ and enter the ____ to form _____; if protoporphyrin is deficient
erythroid precurosrs; mito; heme;
| iron remains trapped in mito
27
P: In sideroblastic anemia, iron-laden mito
form a ring around the nucleus of erythroid precursors, alsoc called RINGED SIDEROBLASTS!!
28
P: How can one get sideroblastic anemia? What do each of these entail?
1. Congential defect most commonly involves ALAS
2. Acquired (alcoholism: mitochondrial poison, lead poisoning: inhibits ALAD and ferrochelatase,
vit B6 deficiency: required cofactor for ALAS, usually a side effect of isoniazid treatment for TB)
29
Sideroblastic anemia lab findings include
increased ferritin, decreased TIBC, increased serum iron, increased percent sat (IRON-OVERLOADED STATE)
30
P: Thalassemia is an anemia due to
decreased synthesis of the globin chains of Hb (decreased globin, decreased Hb, microcytic anemia); an inherited mutation (carriers protected against Plasmodium falciparum malaria)
31
P: Thalassemia is divided into Alpha and Beta based on
decreased production of alpha or beta globin chains (normally HbF, HbA, HbA2 with either two gamma, beta, or delta subunits)
32
P: What is alpha thal usually due to?
Gene deletion on chromosome 16
33
P: For alpha thal, what happens with 1-4 genes being deleted on chromosome 16?
1. One: asymptomatic
2. Two genes: mild anemia with increased RBC count (if cis, associated with increased risk of severe thal in offspring and seen in Asians; if trans, seen more in Africans, espeically in African Americans);
3. Three: severe anema where beta chains form tetramers (HbH) to damage RBC's and HbH seen on electrophoresis
4. Four genes: lethal in utero (hydrops fetalis); gamma chains form tetramers (Hb Barts) to damage RBCs and Hb Barts seen on electrophoresis
34
P: Beta thal is usually due to
gene mutations (point mutations in promoter or splicing sites) seen in individuals of African and Mediterranean descent
35
P: Where are the two beta genes for Hb normally found? Mutations result in ____ or ______ production of globin chain?
found on chromosome 11; absent (B0) or diminished (B+) production of beta-globin chain
36
What is the mildest form of Beta-thal? What do we see?
Beta-thal minor (usually asymp with increased RBC count)
1. microcytic, hypochromic RBCs and target cells seen on blood smear
2. Hb electrophoresis shows slightly decreased HbA with increased HbA2 (5%, normal 2.5%) and HbF (2%, normal 1%)
37
P: What is the most severe form of disease for beta-thal and it presents with...
Beta-thal major (beta0/beta0); severe anemia a few months after birth, with HbF at birth temporarily protective;
38
P: In the most severe form of beta thal, what happens?
1. alpha tetramers aggregate and damage RBC's, resulting in ineffective erythropoiesis and extravascular hemolysis (circulating RBC's remobed by spleen)
2. Massive erythroid hyperplasia ensues resulting in expansion of hematopoiesis into the skull leading to reactive bone formation and crewcut appearance on x-ray, and expansion into facial bones (chipmunk), extramedullary hematopoiesis with HSM, and risk of aplastic crisis with parvovrius B19 infection of erythroid precursors
39
P: What is necessary for severe B-thal and what do labs show?
Chronic transfusions and increased risk for secondary hemochromatosis;
smear shows microcytic, hypochromic RBCs with target cells and nucleated RBC's, and electrophoresis shows HbA2 and HbF with LITTLE OR NO HbA!!!!
40
P: For macrocytic anemias, what are they usually due to and MCV? How are these two things necessary?
Folate or vit B12 deficiency (megaloblastic anemia) with MCV > 100 um3;
Folate circulates in serum as methyl THF and removal of methyl group allows for participation in DNA precursos synthesis; methyl group transferred to vit B12 and vit B12 then transfers the methyl to homocysteine, making methionine
41
P: Lack of folate or vit B12 leads to what?
Impaired DNA precursor synthesis:
1. Impaired division and enlargement of RBC precursors = megaloblastic anemia
2. Impaired division of granulocytic precursors = hypersegmented neutrophils
3. Megaloblastic change also seen in rapidly-dividing epi cells
42
P: Other causes of macrocytic anemia?
Alcoholism, liver disease, and drugs (WITHOUT MEGALOBLASTIC CHANGE)
43
P: How is dietary folate obatined? Where is it absorbed?
Green veggies and some fruits; jejunum
44
P: How does folate deficiency develop? What are some causes? List the clinical and lab findings
Within months (body stores minimal);
poor diet like alcoholics and elderly, increased demand (pregnancy, cancer, hemolytic anemia), and folate antagonists (e.g. methotrexate);
Macrocytic RBC's and hypersegmented neutrophies, glossitis, decreased serum folate, increased serum homocysteine (increased thrombosis risk) and normal methylmalonic acid
45
P: How is vit B12 normally metabolized?
1. Salivary gland enzymes (amylase) liberate B12, which is then bound by R-binder (from salivary gland) and carried through stomach
2. Pancreatic proteases in duodenum detach vit B12 from R-binder
3. Bit B12 binds intrinsic factor (made by gastric parietal cells) in small bowel, and this complex is absorbed in ileum
46
P: Which deficiency is more common? What is most common cause of vit B12 deficiency? Other causes of it?
```
Folate, and vit B12 takes years to develop because of hepatic stores of vit B12;
pernicious anemia (autoimmune destruction of parietal cells leading to intrinsic factor deficiency); include pancreatic insufficiency and damage to terminal ileum (like Crohn disease or Diphyllobothrium latum), with dietary deficiency rare (excpet vegans)
```
47
P: Clinical and lab findings for vit B12 deficiency?
1. Macrocytic RBC's with hyperseg neutrophils
2. Glossitis
3. Subacute combined degen of the spinal cord (vit B12 a cofactor for conversion of methylmalonic acid to succinyl CoA for FA metabolism, but with no B12 you have increased MMA and impaired spinal cord myelinization; damage leads to poor proprioception and vibratory sensation and spastic paresis, due to posterior column and lateral CS tract problems)
4. decreased serum vit B12
5. Increased serum homocysteine (similar to folate deficiency, increasing risk for thrombosis)
6. Increased MMA (UNLIKE FOLATE DEFICIENCY)
48
P: How is normoctyic anemia defined?
Anemia with normal-sized RBCs (80-100) but increased peripheral destruction or underproduction (USE RETIC COUNT TO DESTINGUISH THESE TWO)
49
P: What are reticulocytes and how are they identified? Normal reticu count?
Young RBCs released from bone marrow (on blood smear, they are larger cells with bluish cytoplasm due to residual RNA);
usually 1-2%, replacing the 1-2% of RBCs removed from circulation (after 120 days)
50
P: What happens in anemia with retics?
RC count increases to >3% with functioning marrow, but if there is a decrease in total RBCs, that falsely elevates percentage of retics
51
P: How do you correct for RC values?
Multiply retic count by Hct/45
1. If greater than 3%, good marrow response and peripheral destruction
2. If < 3%, indicates poor marrow response and suggests underproduction
52
P: How are RBC's destroyed?
1. Extravascular: RBC destruction by reticuloendothelial system (macrophages of spleen, liver, lymph nodes); macrophages consume RBC's and break down Hb: globin into aa's, heme into iron and protoporphyrin with iron recycled, and protoporphyrin borken down into unconjugated bilirubin (this is bound to serum albumin and delivered to liver for conjugation and excretion into bile)
2. Intravascular: RBC destruction in vessles
53
Clinical and lab findings of extravascular and intravascular hemolysis
EH: anemia with splenomeg, jaundice due to unconjugated bilirubin, increased risk for bilirubin gallstones
IH: hemoglobinemia, hemoglobinuria, hemosiderinuria (renal tubular cells pick up some of the Hb that is filtered into urine and break it down into iron, which accumulates as hemosiderin, but tubular cells eventually shed --> hemosiderinuria)
decreased serum HAPTOGLOBIN
54
Normocytic anemia with preodominant extravascular hemolysis includes hereditary spherocytosis, which is what?
Inherited defect of RBC cytoskeleton-membrane tethering proteins (usually involves ankyrin, spectrin, or band 3)
55
In hereditary sphero, ___ ___ are formed and lost over time, which leads to whate?
Membrane blebs; losing membrane leads to spherocytes instead of disc-shaped cells, and these spherocytes less able to maneuver through splenic sinusoids and are consumbed by splenic macrophages, resulting in anemia
56
Clinical and lab findings of here sphero? Diagnosis and treatment?
1. Spherocytes with loss of central pallor
2. Increased RDW and increased MCHC
3. typical EH symptoms
4. Increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors;
Diagnose with osmotic fragility test, revealing increased spherocyte fragility in HYPOTONIC solution;
treat with splenectomy, resolving anemia, but spherocytes persist and Howell-Jolly bodies (RBC nuclear frags) emerge on blood smear
57
What is sickel cell anemia, and give some good background facts on it?
Autosomal recessive mutation in beta chain of Hb (single aa change replacing glutamic acid with valine);
gene carried by 10% of individuals of African dscent, likely due to protective role against falciparum malaria;
disease arises when two abnormal beta genes are present, or >90% HbS in RBCs
58
What is the problem with HbS? There is increased risk of ____ with...; what is protective against these negative issues?
Polymerizes when deoxygenated and polymers aggregate into needle-like structures (sickle cells);
sickling with hypoxemia, dehydration, and acidosis;
HbF (at birth, high HbF is protective for first few months of life, and hydroxyurea increases levels of HbF)
59
In sickle cell anemia, cells continuously ____ and _____ which passing through microcirculation; describe the types of hemolysis and what other pathology could ensue
sickle, de-sickle;
EH: as described in normocytic anemia card
IH: RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear;
massive erythroid hyperplasia (like with major beta thal)
60
Irreversible sickling leads to...; list them
complications of vaso-occlusion:
1. dactylitis: swollen hands and feet due to vaso-occlusive infarcts in bones; commonly seen in infants
2. Autosplenetomy (shrunken, fibrotic spleen, leading to increased risk of infection with encapsulated organisms like strep pneumoniae and Haemophilius influenzae, the most common cause of death in children and affected children should be vaccinated by 5 years of age)
3. Acute chest syndrome (vaso-occlusion in pulmonary microcirculation, with chest pain, SOB, lung infiltrates, often precipitated by pneumonia, most common cause of death in ADULT patients)
4. Pain crisis
5. Renal papillary necrosis (results in gross hematuria and proteinuria)
61
What leads to the sickle cell trait? How does it present usually except for...?
Presence of one mutated and one normal beta chain, resulting in t sickle except renal medulla (extreme hypoxia and hypertonicity of medulla causes sickling, resulting in microinfarctions leading to microscopic hematuria and eventually decreased ability to concentrate urine
62
Lab findings of sickle cell anemia?
1. Sickle and target cells seen on blood smear in sickle cell disease, but NOT sickle cell trait
2. Metabisulfite screen causes cells with any amount of HbS to sickle, thus positive in both disease and trait
3. Hb electrophoresis confirms presence and amount of HbS (diseaes 90% HbS, 8% HbF, 2% HbA2; trait 55% HbA, 43% HbS, 2% HbA2)
63
Hb C is a ___ ____ mutation in what? How does this present and what do you see on blood smear?
autosomal recessive in beta chain of Hb (normal glutamic acid replaced by lysin, less common than sickle cell disease);
mild anemia due to EH and see characteristic HbC crystals in RBCs
64
For normocytic anemias with predom IH, what happens with paroxysmal nocturnal hemoglbinuria (PNH)?
Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI) and cells susceptible to destruction by complement
65
Trace steps of PNH and how you get the pathology?
1. Blood cells coexist with complement
2. Decay accelerating factor on surface of blood cells protects against complement-mediated damage by inhibiting C3 convertase
3. DAF secured to cell membrane by GPI
4. Absence of GPI leads to absence of DAF (possible complement-mediated damage)
66
For PNH, when does IH occur?
Episodically, often at night during sleep (mild respiratory acidosis develops with shallow breathing and complement activated; RBCs, WBCs, and platelets lysed, and then see the things associated with IH)
67
For PNH, list screening and comfirmatory tests; main cause of death?; and complications
sucrose test; acidified serum test or flow cytometry to dtect lack of CD55 (DAF);
thrombosis of hepatic, portal, or cerebral veins (destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis);
iron deficiency anemia (due to chronic loss of Hb in urine) and acute myeloid leukemia, which develops in 10% of patients
68
What is G6PD deficiency?
X-linked recessive disorder leading to reduced half-life of G6PD (cells rendered to ixdiatve stress):
1. RBCs normally exposed to oxidative stress, especially H2O2
2. Glutathione (antioxidant) neutralizes H2O2 but becomes oxidized in the process
3. NADPH (by-product of G6PD) needed to regen reduced glutathione
4. Less G6PD, less NADPH, less reduced glutathione, oxidative injury by H2O2, intravascular hemolysis
69
Main G6PD deficiency variants are:
| What is the high carrier freq in the populations most likely due to?
1. African variant (mildly reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress)
2. Mediterranean variant (MARKEDLY REDUCED half-life of G6PD leading to markded intravascular hemolysis with oxidative stress;
protective role against falciparum malaria
70
Oxidative stress precipitates Hb as ___ ____; what can cause this stress, and how can you remove the products formed? WHAT TYPE OF HEMOLYSIS IS SEEN?
Heinz bodies;
infections, drugs (primaquine, sulfa drugs, dapsone) and fava beans;
removed from RBC's by splenic macrophages, resulting in BITE CELLS!!!);
intravascular!
71
How does G6PD deficiency present? What can be used for screening and what can confirm?
```
Hemoglobinuria and back pain HOURS after exposure to oxidative stress;
Heinz preparation (special Heinz stain) and enzyme studies (performed WEEKS after hemolytic episode resolves)
```
72
For immune hemolytic anemia, how is this mediated? Describe the mech's, the associations, and the treatment for each
Antibody-mediated destruction of RBC's;
IgG (usually EH): IgG binds RBCs in warm temp of the central body (warm agglutinin) and membrane of antibody-coated RBC consumed by splenic macrophages --> spherocytes;
2. associated with SLE (most common), CLL, and certain drugs like penicillin and cephalosporins
a. drugs could attach to RBC membrane (penicillin) with subsequent binding of Ab to drug-membrane complex (penicillin)
b. Drug could induce autoAb production to bind self antigens on RBC's (alpha-methyldopa)
3. Treat with cessation of offending drug, steroids, IVIG, and maybe splenectomy;
Also, IgM usually involves IH, with IgM binding RBCs and fixing complement in relatively COLD temp of the extremities, associated with Mycoplasma pneumoniae and infectious mono
73
What can diagnose IHA?
Coombs test (direct or indirect)
1. Direct: confirms presence of antibody-coated RBCs and anti-IgG added to patient RBC's and agglutination occurs if RBC's are already coated with antibody
2. Indirect Coombs: confirms presence of antibodys in patient serum; anti IgG and test RBCs are mixed with the patient serum; agglutination occurs if serum antibodies are present
74
For microangiopathic hemolytic anemia, how does this happen?
IH results from vascular path: RBCs are destroyed as they pass through the circulation (iron deficiency anemia occurs with chronic hemolysis);
can occur with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis (could produce schistocytes on blood smear)
75
What does malaria infect? How is it transmitted?
RBCs and liver with Plasmodium, transmitted by female Anopheles mosquite;
76
In malaria, what happens with RBCs? What could consume these and result in what?
rupture as part of Plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever (P falciparum is daily fever, P vivax and P ovale is fever every other day);
spleen can consume some infected RBCs and result in mild EH with splenomegaly
77
Anemia due to underproduction characterized by what? Some causes??
Decreased RBC production by bone marrow (LOW CORRECTED RETIC COUNT);
causes of microcytic and macrocytic anemia, renal failure (less EPO made by peritubular interstitial cells) and damage to bone marrow precursor cells (maybe anemia or pancytopenia)
78
Examples of anemia due to underproduction? Give the treatment for two of them, and the etiology, what biopsy shows, and treatment for the other
1. Parvovirus B19: infects progenitor red cells and temporarily halts erythropoiesis, leads to significant anemia in the setting of preexisting marrow stress; treatment is supportive
2. Aplastic anemia: damage to hematopoietic stem cells, resulting in PANCYTOPENIA with LOW RETIC COUNT;
causes include drugs or chemicals, viral infections, and auoimmune damage;
biopsy shows empty, fatty marrow;
treatment includes cessation of any CAUSATIVE DRUGS and supportive care with transfusions and marrow-stimulating factors like EPO, GM-CSF, and G-CSF (immunosuppression may be helpful as some cases are due to abnormal T-cell activation with cytokine release, with bone marrow transplant as a last resort)
3. Myelophthisic process: pathologic that replaces bone marrow, with hematopoiesis imparied, resulting in pancytopenia
79
Immune thrombocytopenic purpura: what is happening? What are the forms? List the lab findings and the treatment
1. Autoimmune production of IgG against platelet antigens (e.g. GPIIb/IIIa): MOST COMMON CAUSES of thrombocytopenia in children and adults; the autoantibodies are made by PLASMA CELLS in the spleen, and antibody-bound platelets are consumed by splenic macrophages, leading to thrombocytopenia
2. Acute form (seen in children weeks after viral infection or immunication; self limited, usually resolves within weeks of presentation) vs. chronic (adults mostly, usually women of childbearing age. Could be primary or secondary, and lead to short-lived thrombocytopenia in offspring since antiplatelet IgG can cross placenta!!
3. Labs: low platelets, less than 50 K/uL; normal PT/PTT (coag factors not affected); increased megakaryocytes on bone marrow biopsy
4. Treat with corticosteroids initially: children respond well and adults might show early response, but often relapse;
use IVIG: raises platelet count in symptomatic bleeding but effect is short-lived;
otherwise, use splenectomy to eliminate primary source of Ab and site of platelet destruction (for refractory cases)
80
Microangiopathic hemolytic anemia is what? In what two cases do you see this?
Pathologic formation of platelet microthrombi in small vessels: 1. platelets consumed in formation of microthrombi 2. RBCs "shared" as they cross microthrombi, resulting in HEMOLYTIC ANEMIA with SCHISTOCYTES;
seen in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
81
What is TTP due to? What is HUS due to?
TTP: decreasd ADAMTS13, an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation 1. large, uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi 2. decreased ADAMTS13 usually due to acquired autoantibody, most commonly seen in ADULT FEMALES;
HUS: endothelial damage by drugs or infection 1. look for kids with E coli O157:H7 dysentery, resulting from UNDERCOOKED BEEF 2. E coli verotoxin damages endothelial cells resulting in platelet microthrombi!!
82
Clinical, lab findings, and treatment of HUS and TTP include:
1. Skin and mucosal bleeding
2. Microangiopathic hemolytic anemia
3. Fever
4. Renal insufficiency (more common in HUS: thrombi involve vessels of the kidney)
5. CNS abnormalities (more seen in TTP: thrombi involve vessels of the CNS);
1. thrombocytopenia with increased bleeding time
2. Normal PT/PTT since coag cascade not activated
3. Anemia with schistocytes!!
4. Increased megakaryocytes on bone marrow biopsy;
TREAT: plasmapheresis and corticosteroids, particularly in TTP
83
Hemophilia A: cause, presentation, lab, treatment?
1. Genetic factor VIII deficiency (X-linked recessive and can arise from new mutation without any FH)
2. deep tissue, joint, and postsurgical bleeding (clinical severity depends on degree of deficiency)
3. Labs: increased PTT, normal PT, decreased FVIII, normal platelet count and bleeding time
4. Treatment with recombinant FVIII
84
Hemophilia B (Christmas disease)
Genetic factor IX deficiency;
| resembles hemophilia A, except FIX levels are decreased INSTEAD OF FVIII
85
Von Willebrand Disease: cause, subtypes, presentation, labs, treatment
1. Genetic vWF deficiency (most common inherited coag disorder)
2. Multiple: causes quantitative and qualitative defects; most common is AUTOSOMAL DOMINANT with decreased vWF levels
3. Mild mucosal and skin bleeding; low vWF impairs platelet adhesion
4. Lab findings include: increased bleeding time, increased PTT, normal PT, decreased FVIII half-life, abnormal ristocetin test (this induces platelet agglutination normally by causing vWF to bind platelet GPIb)
5. Use desmopressin, an ADH analog, which increases vWF release from Weibel-Palade bodies of endothelial cells
86
DIC: what does it involve; what is it almost always; labs; treatment
1. pathologic activation of the coag cascade: widespread microthrombi resulting in ischemia and infarction; consumption of platelets and factors results in bleeding, especially from IV sites and mucosal surfaces (bleeding from body orifices)
2. Almost always SECONDARY to another disease process (obstetric complications like tissue thromboplastin in the amniotic fluid activating coagulation; sepsis with endotoxins from bacterial wall and cytokines inducing endothelial cells to make tissue factor, like E Coli or N meningitidis; adenocarcinoma has mucin activate coag; APL: primary granules activate coag; rattlesnake bite: venom activates coag;
3. Labs: decreased platelet count, increased PT and PTT, decreased fibrinogen, microangiopathic hemolytic anemia, elevated fibrin split products, especially D-dimer (this is the best screening test for DIC, derived from splitting of cross-linked fibrin, NOT FIBRINOGEN)
4. Address underlying cause and transfuse blood products and cryoprecipitate (with coag factors) as necessary
87
Robbins: In hemolytic anemias, the phagocytosis of red cells leads to accumulation of the ___ containing pigment _______, particularly in what three organs? What is the term of this particular accumulation? If anemia is severe enough, what can happen?
iron; hemosiderin;
liver, spleen, bone marrow;
hemosiderosis;
extramedullary hematopoiesis: liver, spleen, lymph nodes
88
In the context of sickle cell anemias, red cells in heterozygous individuals
do not sickle except under conditions of profound hypoxia
89
What could efflux of K and H20, along with decrease in pH mean for RBCs?
One leads to RBC dehydration, while another leads to reduced O2 affinity for Hb
90
What three GPI-linked proteins regulate complement activity?
1. Decay-accelerating factor (CD55)
2. Membrane inhibitor of reactive lysis (CD59)
3. C8 binding protein
91
List some clinical conditions that can lead to abnormalities in the vessel wall, leading to bleeding:
1. Infections (e.g. meningococcemia, infective endocarditis)
2. Drug reactions: drug-induced immune complexes in vessel walls, leading to hypersens vasculitis
3. Scurvy and Ehler-Danlos syndrome
4. Henoch-Schonlein purpura: systemic immune disorder characterized by purpuric rash, colicky abdo pain, polyarthralgia, acute glomerulonephritis
5. Hereditary hemorrhagic telangiectasia (autosomal dom)
6. Perivascular amyloidosis
