Disorders of red blood cells, spleen, thymus (Puttoff) Flashcards
what is in the red pulp of the spleen
Constitutional symptoms
fever, night sweats, or weight loss (tuberculosis, lymphoma, or other malignancy)
fever (majority of the infectious diseases)
Use of medications that can cause lymphadenopathy
what is in the white pulp of spleen
where T cells and B cells are located – B cells found in the germinal center
what are the 4 main functions of the spleen
• Phagocytosis of blood cells and particulate matter
• Antibody production
o Antibody secreting plasma cells are the in the sinuses of the red pulp mainly
o Includes antibodies against microbials, and autoantibodies
• Hematopoiesis
o During fetal development – minor site of hematopoiesis
o Compensatory extramedullary hematopoiesis in severe chronic anemia
• Sequestration of formed blood elements
o With splenomegaly→ more platelet mass is held producing thrombocytopenia.
o Enlarged spleen can also trap white blood cells and induce leukopenia
harbors 30-40% of platelet mass in the body (with splenomegaly up to 80-90% of platelets can be sequestered → thrombocytopenia)
what is nonspecific acute splenitis
Enlargement of the spleen in any blood-borne infection
Enlarged spleen and soft
Acute congestion of the red pulp- which can encroach on and efface the lymphoid follicles
Neuts, plasma cells, eosinophils are usually present
When the agent is strep, commonly the white pulp follicles may undergo necrosis
what are the causes of congestive splenomegaly
–Chronic venous outflow obstruction → leads to splenic or portal vein HTN.
–Systemic or central venous congestion → seen in right heart failure
Cirrhosis of liver
Obstruction of extrahepatic portal vein or splenic vein → casued by spontaneous portal vein thrombosis (can be caused by infiltrating tumors from neighboring organs- stomach or pancreas)
what are the findings in congestive splenomegaly
what type of hemolysis might be found?
Marked enlargement of spleen
Thickened and fibrous capsule
Red pulp becomes fibrotic over time
Deposition of collagen in the basement membrane of sinusoids
Because there is slowing of blood flow from the cords to the sinusoids there is prolonged exposure of red blood cells to macrophages→ excessive destruction (hypersplenism)
what is the cause of splenic infarcts…
what do they look like
Usually caused by the occlusion of the major splenic artery
There is lack of collateral blood supply which predisposes the spleen to infarction following vascular occlusion
Bland infarcts→ pale, wedge-shaped, subscapular in location. Capsule is covered with fibrin
Septic infarcts→ suppurative necrosis. Large scars develop with healing
Infarcts are often from the heart**
Common in pt’s who have infectious endocarditis of the mitral or aortic valves
what are the 2 most common types of neoplasms in the spleen
lymphangiomas
hemangiomas
- can be found anywhere in the abdominal cavity
- of great clinical importance in hereditary spherocytosis, and immune thrombocytopenia purpura
accessory spleen
congenital anomaly of spleen
what might cause splenic rupture
are chronically enlarged or acute enlarged spleens more likely to rupture
Usually precipitated by blunt trauma
Spontaneous rupture→ usually there is previously abnormal spleen → infectious mononucleosis, malaria, typhoid fever, lymphoid neoplasms:
- these cause the spleen to enlarge rapidly producing a thin capsule that can rupture easily
- perform splenectomy to prevent death from blood loss
Chronically enlarged spleens are less likely to rupture b/c of toughening/fibrosis of capsule
what types of cells are in the thymus
Thymic epithelial cells (form Hassall’s Corpuscles in medulla),
immature T lymphocytes
morphology of cortical peripheral epithelial cells
polygonal and have abundant cytoplasm with dendritic extensions.
morphology of medulla epithelial cells
Medulla epithelial cells are densely packed and have spindle-shaped, scant cytoplasm, no interconnecting processes
thymic hypoplasia
DiGeorge syndrome- defects in cell mediated immunity and variable abnormalities of parathyroid development , 22q11 deletion
thymic cysts
- what lines these cysts
- what should you do if you find a cyst
discovered incidentally
- rarely exceed 4 cm
- lined by stratified to columnar epithelium
***presence of a cystic thymic lesion in a symptomatic pt should provoke a thorough search for a neoplasm (thymoma or lymphoma)
what occurs with thymic hyperplasia
what types of diseases/settings does this occur in
what are these often mistaken for
Appearance of B cell germinal centers within the thymus- thymic follicular hyperplasia
Occurs in:
- chronic inflammatory states
- Myasthenia gravis- 65-70% of cases
- SLE
- Graves
- RA
- Sclerodoma
May be mistaken radiologically for a thymoma leading to unnecessary surgical procedures
what cell type makes up thymomas
thymic epithelial cells
what are the clinical features, etiology and location of thymomas
In all categories:
- adults older than 40
- rare in children
- males = females
- most arise in anterior superior mediastinum**
- sometimes occur in neck, thyroid, pulmonary hilus, or elsewhere
- uncommon in posterior mediastinum
40% present with symptoms stemming from impingement on mediastinal structures***
Another 35-40% are detected in the course of evaluating pt’s with myasthenia gravis ***
22q11 deletion
DiGeorge syndrome
tumors that usually have a substantial portion of medullary type epithelial cells are usually
noninvasive
medullary type epithelial cells or mix of medullary type + cortical type
sparse infiltrates of thymocytes
makes up 50% of thymomas
tumors that are cytologically benign and non invasive
thymoma
penetrates through the capsule into surrounding structures
epithelial cells are more likely to be cortical type –> abudant cytoplasm, rounded vesicular nuclei and mixed with numerous thymocytes
neoplastic cells may show atypia
20-25% of all thymomas
Tumors that are cytologically benign but invasive or metastatic
what are the survival rates for tumors that are cytologically benign but invasive or metastatic
Extensive invasion → 5 year survival of less than 50%
With minimal invasion, complete excision yields 5 year survival of >90%
Tumors that are cytologically malignant (thymic carcinoma)
5% of thymomas
Fleshy, invasive masses, sometimes accompanied by metastases to sites like lungs
- Most are squamous cell carcinomas
- About 50% of these contain monoclonal EBV genomes
Atypia
what is anemia
Defined as a reduction of the total circulating red cell mass
Reduction in oxygen carrying capacity → tissue hypoxia
Usually diagnosed based on reduction in hematocrit and the hemoglobin concentration
MCV >100
MCV <80
macrocytosis
microcytosis
what are the signs/symptoms of anemia
Pale
Weakness
Malaise
Easy fatigability
Dyspnea on mild exertion due to lowered O2 content
Hypoxia→ fatty changes in the liver, myocardium and kidney
Cardiac fatty changes can lead to cardiac failure and further hypoxia→ angina pectoris
Central nervous system hypoxia can cause headache, dimness of vision and faintness
what occurs in acute blood loss?
what is seen in lab studies?
what type of anemia is this ?
Loss of fluid leads to shift in fluids from the interstitial fluid compartment → reduced hematocrit and hemodilution
Blood loss = decreased O2 content→ release of EPO from kidney → proliferation of committed erythroid progenitors (takes about 5 days for newly synthesized reticulocytes to appear in PB)
The effects of acute blood loss are mainly due to loss of intravascular volume, which if massive can lead to cardiovascular collapse, shock and death
Significant bleeding results in changes in blood involving red cells AND white cells and platelets.
Significant blood loss→ decrease in blood pressure→ adrenergic hormone release → mobilization of granulocytes → leukocytosis
Thrombocytosis
Usually starts as normocytic normochromic anemia → later on more reticulocytes appear (macrocytosis)
what is extravascular hemolysis
what are the clinical findings?
Caused by:
• Alterations that render the red cell less deformable
destruction of red cells in
phagocytes→
anemia,
splenomegaly,
jaundice,
variable decreases in haptoglobin
what is intravascular hemolysis
what are the clinical findings?
caused by:
•mechanical injury→ cardiac valves, thrombotic narrowing of microcirculation, bongo drum beating, marathon running
- complement fixation- antibodies bind red cell antigens
- intracellular parasites
- exogenous toxic factors
Findings: -anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, jaundice -splenomegaly is not seen***
why does renal hemosiderosis occur
accumulation of iron released from hemoglobin accumulating in renal tubular cells
why does urine turn brown with hemolytic anemias?
As serum haptoglobin is used up to sequester free hemoglobin, the remaining free hemoglobin oxidizes to methemoglobin = brown in color→ can make urine turn red brown
what are the lab findings in hemolytic anemias?
- increased numbers of erythroid precursors (normoblasts) in marrow
- reticulocytosis in PB
- hemosiderin (iron containing pigment) in the spleen, liver, BM = hemosiderosis
- Extramedullary hematopoiesis if anemia severe (in liver, spleen, lymph nodes)
- Pigment gallstones–> due to excessive bilirubin excreted by the liver into the GI tract and converted to urobilin
what are the 3 shared features in all hemolytic anemias
- Short red cell life span
- Elevated EPO
- Accumulation of hemoglobin degradation products
pt’s often benefit from splenectomy
Caused by intrinsic defects in red cell membrane skeleton that render red cells spheroid, less deformable, and vulnerable to splenic sequestration and destruction
Autosomal dominant (75%) Remaining cases are compound heterozygosity (inheritance of 2 defects)
Can turn into an aplastic crisis
mutations: ankyrin band 3 spectrin band 4.2
results in failure to produce any protein–> destabilizes the plasma membrane
Morphology: dark staining red cells lacking central zone of pallor -reticulocytes -marrow hyperplasia -mild jaundice
Clinical features:
Northern europe descent
moderate splenomegaly ***
extravascular hemolysis
***increased MCHC
Anemia, splenomegaly, jaundice triad ***
Hereditary spherocytosis
what is an aplastic crisis
triggered by parvovirus
Parvovirus → infects and kills red cell progenitors causing red cell production to cease. Because of the reduced life span of HS red cells, cessation of erythropoiesis for even short time periods leads to sudden worsening of the anemia. Transfusions may be necessary to support the patient until the immune response clears the infection.
Recessive X-linked trait (M>F)
results in decreased generation of NADPH and therefore reduced glutathione which protects against oxidant injury by participating as a cofactor in the rxns that neutralize compounds such as H2O2
older cells unable to tolerate oxidative stress
Causes:
drugs- sulfa, primaquine (malaria drugs)
infections
foods
Heinz bodies
Bite cells
begins 2-3 days after exposure to oxidants
Splenomegaly and cholelithiasis are ABSENT
G6PD deficiency
X-linked!!!
Both intravascular and extravascular hemolysis
Protect against malaria by increasing the clearance and decreasing the adherence of infected red cells, possibly by raised levels of oxidant stress and causing membrane damage in the parasite-bearing cells
what is the genetic defect in sickle cell disease
what does this mutation promote
substitution of valine for glutamic acid at position 6 of the beta chain
Mutation promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction and ischemic tissue damage
sickle cell trait
8-10% of African Americans are heterozygous for HbS (offspring of 2 heterozygotes has ¼ chance of having sickle cell disease)
sickle cell disease
almost all of the Hgb in red cell is HbS (SS)
90% HbS
8% HbF
2% HbA
less severe if HbF remains
how is the definitive diagnosis of sickle cell made
hemoglobin electrophoresis
when do heterozygotes sickle?
-Heterozygotes only sickle under conditions of profound hypoxia
what is the effect of HbA on sickling
-HbA→ interferes with HbS polymerization
what is the effect of HbF on sickling
-HbF→ inhibits polymerization of HbS even more than HbA so infants aren’t symptomatic until 5-6 months when the level of HbF falls. Hereditary persistence of HbF = less severe sickling
HbS and HbC compound heterozygotes
(HbSC disease) have symptomatic sickling disorder but milder than sickle cell disease (Than straight SS)
increase in MCHC has what effect on sickling
decrease in MCHC?
Mean cell hemoglobin concentration
→ increase in MCHC (dehydration) = facilitates sickling
→ decrease in MCHC = reduce disease severity (individual with HbS homozygote AND alpha thalassemia)
effect of intracellular pH on sickling
-decrease pH→ reduce O2 affinity of hemoglobin → increase deoxygenated HbS→ more sickling
transit time has what effect on sickling
Transmit time of red cells through microvascular beds
SLOW = more sickling (bone marrow, spleen, inflamed vascular beds)
Morphology in sickle cell disease
Sickled cells
Reticulocytosis
Target cells
Howell-Jolly bodies
how does sickle cell protect against malaria
intracellular parasites consume O2 and decrease intracellular pH→ promotes hemoglobin sickling in AS red cells. These cells are stiff and distorted and may be cleared more rapidly by phagocytes in the spleen, liver, keeping parasite load down
by what 2 mechanisms do microvascular occlusions occur in sickle cell disease
inflammation** and vasoconstriction play a role.
Inflammatory states produced mediators that up-regulate adhesion molecules on endothelial cells→ more likely that sickled red cell gets stuck
Depletion of NO** due to inactivation by free hemoglobin released from lysed sickled red cells
what are vaso-occlusive crises
what organs systems are involved
how do pt’s present
(children, males?)
aka pain crises, are episodes of hypoxic injury and infarction that cause severe pain in the affected region
o infection, dehydration and acidosis all favor sickling and can act as a trigger
o involves bones, lungs, liver, brain, spleen and penis
• in children → manifests as hand-foot syndrome or dactylitis of hands and/or feet
o Priapism: hypoxic damage and erectile dysfunction
o loss of visual acuity –retinopathy
o stroke→ adhesion of sickle red cells to arterial vascular endothelium and vasoconstriction due to depletion of NO by free hemoglobin
o crippling
chest pain SOB lung infiltrates often precipitated by pneumonia most common cause of death in adult pt's with sickle cell disease
• Acute chest syndrome: vaso-occlusive crisis involving the lungs
occur in children with intact spleens with sickle cell disease
Massive entrapment of sickled red cells leads to rapid splenic enlargement, hypovolemia, and sometimes shock. Requires transfusions
sequestration crises
what disease are associated with aplastic crises
sickle cell disease
hereditary spherocytosis
what are the effects of chronic sickle cell disease
→ impairment of growth and development and organ damage affecting the spleen, heart, kidneys, and lungs.
o Hypertonicity in the renal medulla provokes sickling→ leads to hyposthenuria (inability to concentrate urine) → even more dehydration
what are sickle cell pt’s susceptible to ?
infection with encapsulated organisms due to altered spleen fn: . Pneumococcus pneumoniae and Haemophilus influenzae septicemia and meningitis
b/c of autosplenectomy
disorder of decreased platelet survival- platelet functions are normal
caused by autoantibody mediated destruction of platelets
F>M (Women less than 40 years old)
splenomegaly and LAD are uncommon!
how do you treat?
Chronic immune thrombocytopenic purpura
treatment–> splenectomy
platelets are destroyed in the spleen after being coated with antibodies to platelet membrane glycoproteins IIb/IIIa or Ib-IX
spleen is the source of the antibodies and the site of destruction!
IgG antibodies active at 37C
splenomegaly
warm antibody type
IgM antibodies active below 37C
IgM bindings–> agglutinates red cells–> fixes complement (C3b) –> phagocytosis by spleen, liver, bone marrow ]]
appears sometimes after infection (mycoplasma pneumoniae, EBV-mono, influenza virus, cytomegalovirus , HIV)
pallor, cyanosis, Raynaud phenomenon
Cold agglutin type
15-30% of cases
meningococcemia
rickettsioses
Vitamin C deficiency
henoch-schonlein purpura
Hereditary-Hemorrhagic telangiectasia
Perivascular amyloidosis
platelet number and function normal
PT and PTT normal
Bleeding disorders caused by vessel wall abnormalities
Cold agglutinin immunohemolytic anemia can be seen with lymphoid neoplasms and infections such as what
Mycoplasma EBV-mono Cytomegalovirus Influenza virus HIV
small, round inclusions in RBC’s that appear when the spleen is absent
howell jolly bodies
teardrop cells
myelofibrosis and other infiltrative disorders of the marrow
macro-ovalocytes
seen in megaloblastic anemias - such as Vitamin B12 deficiency
what are the causes of warm antibody type immunohemolytic anemia
idiopathic –> 50%
predisposing condition (SLE, lymphoid neoplasm)
drug exposure (alpha-methyldopa, penicillin, cephalosporin)
positive coombs test
presence of anti-RBC antibodie s in the serum and on the surface of RBC
ristocetin dependent bioassay that is low
vWF deficiency
most cases its autosomal dominant
how do you treat vWF deficiency
demopressin - stimulates vWF release
infusions of plasma concentrates containing factor VIII and vWF
hydroxyurea therapy in sickle cell disease has what benefits/outcomes?
inhibitor of DNA synthesis –> increases HbF levels and has anti-inflammatory effect
HbF interferes with HbS polymerization
x-linked disorder
10% of African American males
manifests after –> primaquine, sulfonamides, nitrofurantoin, phenacetin, aspirin
heinz bodies
G6PD deficiency
increased ferritin
reduced TIBC
anemia of chronic disease
IL-6 promotes sequestration of storage iron with poor use for EPO
EPO secretion is impaired
what are the causes of aplastic anemia
Acquired
- idiopathic- 65%***
- immune mediated
Chemical agents
- benzene
- chemotherapy agents
- chloramphenicol
- gold salts
physical agents
- viral infections
- whole body irradiation
inherited
- Fanconi anemia
- telomerase defects
autosomal recessive
defects in multiprotein complex required for DNA repair
evident early in life
usually present with hypoplasia of kidney, spleen, bone anomalies (thumbs)
Fanconi anemia (cause of aplastic anemia)
abnormally short telomeres
found in half of pt’s with aplastic anemia
hypocellular bone marrow
many fat cells
fibrous stroma
scattered lymphocytes and plasma cells
dry tap
abnormal bleeding
occurs at any age M=F
insidious
pancytopenia
no splenomegaly
Aplastic anemia
what is the treatment for aplastic anemia and what is the prognosis
BM transplant - 5yr survival of more than 75%
immunosuppressive therapy
fever
thrombocytopenia
microangiopathic hemolytic anemia (schistocytes)
transient neurologic deficits (headaches, photophobia, disorientated)
renal failure (elevated creatinine)
thrombotic thrombocytopenic purpura
deficiency in plasma enzyme ADAMTS13 (vWF metalloprotease) –> normally degrades very high molecular weight multimers of vWF but in its absence these multimers accumulate in plasma –> platelet activation/aggregation
heart, brain and kidney are most often affected
PIGA gene
CD55
CD59
C8 binding protein
X-linked
paroxysmal nocturnal hemoglobinuria
*** only hemolytic anemia caused by acquired genetic defect
mutation in PIGA–> PIGA is an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory proteins
PNH blood cells are deficient in GPI-linked proteins that regulate complement activity
1) Decay-accelerating factor (CD55)
2) Membrane inhibitor of reactive lysis (CD59) **most important b/c this is a potent inhibitor of C3 convertase that prevents spontaneous activation of alt. complement pathway
3) C8 binding protein
what is the mechanism of injury in PNH
Mechanism of injury:
Red cells deficient in
←GPI-linked proteins are susceptible to lysis by complement → manifests as intracellular hemolysis (due to C5-C9 MAC)
**nocturnal portion of disease is due to slight decrease in blood pH during sleep → increases the activity of complement
what is the leading cause of death in PNH
what other problem can develop/occur in PNH
thrombosis
-40% have venous thrombosis (hepatic, portal, cerebral veins)
5-10% develop AML or myelodysplastic syndrome
how do you diagnose PNH
flow cytometry
how do you treat PNH
Eculizumab = monoclonal antibody that prevents conversion of C5 to C5a- lowers risk of thrombosis and reduces hemolysis
Adverse effects: increased risk of serious meningococcal infections
A 42-year-old woman has had nosebleeds, easy bruising, and increased bleeding with her menstrual periods for the
past 4 months. On physical examination, her temperature is 37°C, pulse is 88/min, respirations are 18/min, and blood
pressure is 90/60 mm Hg. She has scattered petechiae over the distal extremities. There is no organomegaly. Laboratory
studies show hemoglobin of 12.3 g/dL, hematocrit of 37%, platelet count of 21,500/mm3, and WBC count of 7370/mm3. A
bone marrow biopsy specimen shows a marked increase in megakaryocytes. The prothrombin and partial thromboplastin
times are within the reference range. What is the most likely diagnosis?
idiopathic thrombocytopenic purpura
where is Vit B12 absorbed
terminal ileum
Causes:
1) associated with defects in complement factor H
membrane cofactor protein (CD46) or factor I
these are all important in preventing excess activation of the alternative complement pathway
2) acquired antibodies
remitting relapsing course
prominence of renal failure
PT and PTT normal
Atypical hemolytic uremic syndrome
associated with infectious gastroenteritis caused by E.coli strain O157;H7→ elaborates shiga-like toxin which alters endothelial cell function resulting in platelet activation
- children and older adults
- bloody diarrhea
- supportive care
- irreversible renal damage and death can occur
typical HUS
TNF
implicated in DIC occurring with sepsis
induces endothelial cells to express TF
decreased thrombomodulin
upregulates expression of adhesion molecules on endothelial cells
A 17-year-old boy reports passage of dark urine to his physician. He has a history of multiple bacterial infections and
venous thromboses for the past 10 years, including portal vein thrombosis in the previous year. On physical examination,
his right leg is swollen and tender. CBC shows hemoglobin, 9.8 g/dL; hematocrit, 29.9%; MCV, 92 μm3; platelet count,
150,000/mm3; and WBC count, 3800/mm3 with 24% segmented neutrophils, 1% bands, 64% lymphocytes, 10%
monocytes, and 1% eosinophils. He has a reticulocytosis, and his serum haptoglobin level is very low. A mutation affecting
which of the following gene products is most likely to give rise to this clinical condition?
□ (A) Spectrin □ (B) Glucose-6-phosphate dehydrogenase □ (C) Phosphatidylinositol glycan A (PIGA) □ (D) β-Globin chain □ (E) Factor V □ (F) Prothrombin G20210A
□ (C) Phosphatidylinositol glycan A (PIGA)
A mutation in this gene prevents the membrane expression of
certain proteins that require a glycolipid anchor. These include proteins that protect cells from lysis by spontaneously
activated complement. As a result, RBCs, granulocytes, and platelets are exquisitely sensitive to the lytic activity of
complement. The RBC lysis is intravascular; patients can have hemoglobinuria (dark urine). Defects in platelet function
are believed to be responsible for venous thrombosis.
Laboratory studies show hemoglobin of 8.8 g/dL, hematocrit of 26.3%, platelet count of 199,000/mm3, and
WBC count of 5350/mm3.
α-Globin inclusions are present in erythroblasts and erythrocytes, leading to increased
phagocytosis by cells of the mononuclear phagocyte system.
B-thalassemia
form of marrow failure in which space occupying lesion replaces normal marrow elements
most common causes:
-metastatic cancer (breast, lung, prostate)
can be a component of the spent phase of myeloproliferative disorders
Myelophthisic anemia
marrow distorition and fibrosis
abnormal release of nucleated erythroid precursors and immature granulocytic forms (leukoerythroblastosis)
tear drop shaped red cells (deformed during escape from the fibrotic marrow)
Esophageal webs
Microcytic hypochromic anemia
Atrophic glossitis
Pulmmr -Vinson syndrome
chronic Iron deficiency anemia
stillbirths
thalassemia major
caused by autoantibodies to platelets (decreased platelet survival)
disease of childhood
M=F
followed viral illness
treatment with glucocorticoids
Acute immune thrombocytopenia purpura
A 77-year-old man has experienced increasing malaise and a 6-kg weight loss over the past year. He has noted more
severe and constant back pain for the past 3 months. On physical examination, his temperature is 38.7°C. His prostate is
firm and irregular when palpated on digital rectal examination. There is no organomegaly. A stool sample is negative for
occult blood. Laboratory studies include a urine culture positive for Escherichia coli, serum glucose of 70 mg/dL,
creatinine of 1.1 mg/dL, total bilirubin of 1 mg/dL, alkaline phosphatase of 293 U/L, calcium of 10.3 mg/dL, phosphorus of
2.6 mg/dL, and PSA of 25 ng/mL. CBC shows hemoglobin, 9.1 g/dL; hematocrit, 27.3%; MCV, 94 μm3; platelet count,
55,600/mm3; and WBC count, 3570/mm3 with 18% segmented neutrophils, 7% bands, 2% metamyelocytes, 1%
myelocytes, 61% lymphocytes, 11% monocytes, and 3 nucleated RBCs per 100 WBCs. What is the most likely diagnosis?
□ (A) Anemia of chronic disease
□ (B) Aplastic anemia
□ (C) Hemolytic anemia
□ (D) Megaloblastic anemia
□ (E) Myelophthisic anemia
□ (F) Thalassemia
(E) This patient has findings most suggestive of prostatic adenocarcinoma that has metastasized to the bone. High
alkaline phosphatase, hypercalcemia, and a leukoerythroblastic pattern in the peripheral blood (immature WBCs and
RBCs) are a consequence of the tumor acting as a space-occupying lesion. Myelophthisic anemias also may be caused
by infections.
what are the effects of having SLE hematologically
low haptoglobin b/c SLE is an autoimmune disease that can result in hemolysis by means of autoantibodies directed at RBC’s and the Coombs test is often positive
interleukin-1, tumor necrosis factor, and
interferon-γ
low EPO
low serum iron
high ferritin
reduced TIBC
These cytokines promote sequestration of iron in storage compartments and depress erythropoietin
anemia of chronic disease
-most common cause of anemia in hospitalized pt’s in US
IL-6
stimulates increase in hepatic production of hepcidin
leukoerythroblastosis,
Metastases are space-occupying lesions (myelophthisic process)
The absence of ADAMTS-13 …
The absence of ADAMTS-13 gives rise to large multimers of vWF that promote widespread platelet aggregation,
and the resulting microvascular occlusions in brain, kidney, and elsewhere produce organ dysfunction, thrombocytopenia,
microangiopathic hemolytic anemia (MAHA), and bleeding.
deffective aggregation
-auto recessive
- fail to aggregate in response to ADP, collagen, epi, thrombin b/c of deficiency of glycoprotein IIb-IIIa→ an integrin that participates in “bridge formation” b/w platelets by binding fibrinogen
- severe bleeding
Glanzmann thrombasthenia
Hepcidin levels increase when
iron stores are high.
excessive iron absorption
palpable spleen tip
high serum ferritin
beta-thal
what can PNH develop into
AML
myelodysplastic syndrome
