Chapter 14 Red Blood Cell and Bleeding Disorders Flashcards
1
Q
What is anemia?
A
-reduction of the total circulating red cell mass below normal limits
2
Q
How does anemia present?
A
- weakness, malaise, easily tired
- hypoxia can cause fatty change in liver, heart and kidney
3
Q
What are anemias of blood loss?
A
loss of intravascular volume
it takes 5 days for CFU-Es to mature
fluid rapidly replenishes from interstitial fluid
4
Q
What is a complication of early blood loss recovery?
A
Thrombocytosis (increase in platelet production)
5
Q
Hemolytic Anemias share what three features?
A
1-shortened red cell life below 120 days
2-elevated erythropoietin
3-build up of hemoglobin breakdown products from hemolysis
6
Q
What are the main clinical features of extravascualr hemolysis?
A
anemia, splenomegaly, and jaundice
7
Q
Does haptoglobin increase or decerease in hemolytic anemia? What does it do?
A
decreases because it binds to the free hemoglobin that overflows from macrophages doing the lysing of red blood cells
8
Q
What is intravascular hemoylsis?
A
hemolysis from physical damaged like from a parasite
9
Q
What are the manifestations of intravascular hemolysis
A
anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, and jaundice
10
Q
What is Hereditary Spherocytosis?
A
- inherited disorder of intrinsic defect in the red cell membrane skeleton
- renders cells spheroid and less deformable increasing their chances to break or become lodges in the spleen
11
Q
What is the pathogenesis of Hereditary Spherocytosis (HS)?
A
- Spectrin dimer self associates into a tetramer
- Ankyrin binds spectrin
- Glycophorin A binds spectrin
12
Q
How does HS clinically present?
A
- Diagnose on: Family History, labs, blood findings
- 2/3 of patients are sensitive to osmotic lysis w/ hypotonic salts
- HS red cells have increased mean cell hemoglobin concentration
- anemia, splenomegaly, and jaundice
13
Q
What is the danger of parvovirus?
A
- may cause aplastic crisis b/c it lyses red blood cells and shuts off RBC production for about 2 weeks
- transfusion may be needed to help patient live
14
Q
Hemolytic Disease Due to Red Cell Enzyme Defects: Glucose-6-Phosphate Dehydrogenase Deficiency is defined as what?
A
-abnormalities in the hexose monophosphate shunt or glutathione metabolism resulting from deficient or imparied enzyme function reduce the ability of red cells to protect themselves against oxidative injuries and lead to hemolysis
15
Q
G6PD is supposed to do what?
A
- reduce NADP to NADPH
- NADPH is supposed to convert oxidize glutathione to reduce glutathione
16
Q
What populatio has a higher incidence of G6PD deficiency?
A
places where malaria is an issue (plasmodium flaciparum)
17
Q
________ hemolysis is characteristic of G6PD deficiency that can be triggered by infections, microaggressions, and donald trump
A
episodic
18
Q
What bodies are found with G6PD?
A
Heinz bodies which are membrane bound bodies
19
Q
What is Sickle cell anemia?
A
a point mutation in the sixth codon of B-globin (glutamate for valine) that promotes the ploymerization of deoxygenateed hemoglobin leading to RBC distortion, hemolytic anemia, microvascular blockage, and ischemic tissue damage
20
Q
How does sickle cell protect against malaria?
A
- Sickle cells cant be infected
- malaria lowers INTRAcellular pH causing the cell to sickle
- sickled cells are readily cleared more easily by spleen and liver
- sickled cells prevent PfEMP-1 knobs from adhering cells to epithelium
21
Q
Heterozygotes of sickle cell on sickle when?
A
they experience hypoxia
22
Q
What interfers with the sickle of cells?
A
HbF stops HbS from sickling cells until a child is bout 5 years old
23
Q
What factors help sickle blood?
A
- HbS concentration
- Intracellular pH drop
- Increased transit time through kidney
24
Q
How does sickle cell present clinically?
A
- moderate to severe hemolytic anemia
- episodes of hypoxic injury and pain–bones, penis, brain, spleen (pain more common in kids)
- presence of irreversible sickled cells
- sausage fingers and toes (dactylitis)
- reticulocytosis
- hyperbilirubinemia
25
Acute chest syndrome is what?
- dangerous type of vaso-oclusive crisis in the LUNGS
| - fever, cough, chest pain, pulmonary infiltrates
26
What is priapism?
-prolonged erection associated with 45% of sickle men after puberty
27
What is Sequesteration crisis?
happens in kids with intact spleens
| spleen gets blocked leading to hypovolemia
28
What is aplastic crisis?
-parvovirus B19 lysing RBCs and shutting off RBC production for 2 weeks
29
Chronic subtle hypoxia can cause what?
stunted growth and development of body and organs
30
Asplenia leads you at risk of what infections?
- capsulated organism infection
- Penumococcus pneumoniae
- Haemophilus influenzae
31
What are thalassemia disorders?
- autosomal dominant
- spikey hair crew cut bone on xray
- deficit of HbA hemoglobin synthesis
- alpha/beta mutation = reduced hemoglobin synthesis
- microcytic hypochromic anemia is the end result
- RBC membranse unstable = lyse = ineffective hematopoiesis = extravascular hemolysis
32
Whats the pathogenesis of B-Thalassemia?
- mutation that diminish synthesis of B-globin chanins
- can be beta0 or beta+
- beta0 = no globin synth (chain terminator/splice mut)
- beta+ = reduced globin synth (promoter/splice mut)
- splicing mutation is the most common
33
How does B-Thalassemia present?
- if have two B alleles patient is transfusion dependent AKA termed thalassemia major
- if have one B allel patient has mild asymptomatic microcytic anemia AKA thalassemia minor
34
What is alpha-Thalassemia?
-inherited deletions that result in reduced or absent synthesis of alpha-globin chains
35
What are the clinical syndromes for alpha-thalassemia?
- each of the four alpha-globin genes contribute 25%. the more that are mutated the worse it is
- Silent carrier state = asymptomatic w/ microcytosis
36
What is the alpha thalassemia trait?
- 2 alphas are deleted
- asians have 2 a's deleted on 1 chr = symptoms
- blacks have 1 a's deleted on 2 chrs = asymptomatic
- HbA lvls normal to low
- small red cells (microcytosis)
- minimal to no anemia
37
What is hemoglobin H disease?
- 3 a's are deleted
- creates HbH = high O2 affinity
- leads to hypoxia
- HbH = RBC inclusions = spleen kills RBCs = severe anemia
38
What is Hydrops Fetalis?
- all 4 a's deleted
- fetus in trouble by 3rd trimester
- death or life long dependence on transfusions
- hematopoietic stem cell transplant may be curative
39
What is paraoxysmal Nocturnal Hemoglobinuria (PNH)?
- X-linked Mutations inactivate PIGA
- GPI-linked proteins are deficient b/c of the mutation
- an enzyme that is essential for the synthesis of membrane bound proteins
- only hemolytic anemia caused by genetic defect
40
What are the CD markers for paraoxysmal nocturnal hemoglobinuria (PNH)?
decaying factor CD55
lysis inhibitor CD59
C8 binding protein CD59
41
Red blood cells deficient in CD55, CD59, and C8 are prone to what?
cell lysis
42
What is the leading cause of death in PNH patients?
- thombosis on the venous variety
| - 10% progress to acute myeloid luekemia
43
How is PNH diagnosed?
flow cytometry which detects deficiencies in GPI-linker proteins such as CD59
44
What reduces the C5a complement pathogenesis of PNH?
Eculizumab stops conversion of 5 to 5A
45
What do cells lyse at night in PNH?
- the blood pH drops slightly during sleep which increases the activity of complement
- loss of heme in pee = iron deficiency = anemia
46
Prognosis of PNH?
Good, can be cured with hematopoietic stem cell transplant
47
What are immunohemolytic anemias?
-antibodies bind to RBCs leading to their destruction
48
How are immunohemolytic anemias diagnosed?
detection of antibodies and/or complement on red cells from the patient
-Use direct Coombs antiglobulin test
49
What the indirect Coombs test do?
- patients serum tested for its ability to applutinate commercially available RBCs bearing particular defined antigens
- used to determine antigen target
- used to determine temp dependence of antibody
50
Cold agglutinin antibodies active under 37 degrees?
IgM
mono, mycoplasmal infxn
chronic--lymphoid neoplasms
chronic--idopathic
51
Warm agglutinin antibodies active above 37 degrees?
IgG
primary--idiopathic
secondary-- autoimmune, drugs, lymphoid
52
Cold hemolysin type active above 37 degrees
IgG
RARE
in kids after viral infection
53
What are megaloblastic anemias?
- deficiencies of folate of B12 = defective DNA synth
- ineffective hematopoiesis
- B12 deficient = neuro damage
- abnormally large erythroid precursors and red cells
54
What requires folic acid and B12 in order to be synthesized?
thymidine
55
Anemias of Vitamin B12 Deficiency: Pernicious Anemia is defined as what?
-caused by autoimmune gastritis = impaired intrinsic factor (IF) secretion by pareital cells in fundic mucosa = impaired B12 uptake
56
What is pernicious anemia's population? pathogenesis?
- whites especially Scandinavians
- usually older than 60yrs
- chronic autoimmune gastritis
- 75% have antibody 1 = block B12 and IF from binding
- type 2 antibody = stop IF and B12 binding to ileal receptor
- 85% type 3 = ?
57
How does pernicious anemia present clinically?
- insidious onset
- mod-sev megaloblastic anemia
- low serum B12
- high serum homocysteine & methylmalonic acid
- hypersegmented granulocytes
58
How is pernicious anemia diagnosed?
-reticulocytes and hematocrit rise after 5 days of B12 supplements
-patients have increased risk of gastric carcinoma
homoxcysteine = risk for thrombosis & atherosclerosis
-TX cures neuropathy progression but doesnt reverse gastric cancer chances
59
Anemia of Folate Deficiency's suppressed synthesis of DNA is the common denominator of _______ and _____, is the immediate cause of _________
folic acid and B12 deficiency
| megaloblastosis
60
Who is at risk of Folate deficiency?
poor vegan diets
pregnancy
cancer
61
Iron absorption is regulated by what?
-hepcidin, a small circulating peptide that is synthesized and released from the liver in response to increases in intrahepatic iron levels
62
What happens when TMPRSS6 is mutated?
-rare form of microcytic anemia that suppresses hepcidin production
63
hepcidin activity is inappropriately low in what?
primary and secondary hemochromatosis
64
What are 4 causes of iron deficiency?
1-dietary lack
2-impaired absorption
3-increased requirement
4-chronic blood loss
65
How much iron do you need a day?
1mg a day absorbed so we need to eat about 10mg due to the 10% absorption rate
66
What is the pathogenesis of iron deficiency?
hypochromic microcytic anemia
67
What are the clinical features of iron deficiency?
- Pica, Plummer-Vinson Syndrome
- alopecia
- atrophic tongue and gastric mucosa
- iron supplements fix this in 5-7 days
68
What is anemia of chronic disease?
impaired RBC production w/ chronic inflammation
69
What three chronic illnesses are related to anemia of chronic disease?
1-chronic microbial illness
2-chronic immune disorders
3-neoplasms
70
What does aplastic anemia refer to?
a syndrome of chronic primary hematopoietic failure and attendant pancytopenia
71
What are come causes of aplastic anemia?
- viral infxns (hepatitis)
- Whole-body irradiation (Chernobyl)
- Fanconi Anemia (thumbs and radii anomalies)
- inherited telomerase defect (adult onset)
72
What is the pathogenesis of aplastic anemia?
- two major etiologies have been invoked: an extrinsic, immune-mediated suppression of marrow progenitors, and an intrinsic abnormality of stem cells
- TH1 cells and TNF mutations kill RBC progenitors
- TX immunosuppressive drugs help (cyclosporine)
73
What is the clinical presentation of aplastic anemia?
- insidious onset
- pancytopenia
- thrombocytopenia = bruising and petechiae
- ABSENT splenomegaly
- marrow is hypocellular
- Prognosis = BAD 5yr survival w/ TX
74
What is Acute Pure Red Cell Aplasia?
Acute: parvovirus B19 infection
Chronic: neutralizing antibodies against erythropoitin
Chronic: thymomoa
Chronic: large granular lymphocytic leukemia
75
What is myelophthisic anemia?
space ocupying lesions replace normal marrow elements
76
What is the most common cause of myelophthisic anemia?
metastatic cancer from boobs, prostate, lungs
77
Chronic Renal Failure is almost always accompanied by ________?
anemia that tends to be roughly proportional to the severity of the uremia
78
What type of anemia do endocrine disorders give you?
i. e. hypothyroidism
| - mild normochromic, normocytic anemia
79
What is polycythemia?
- abnormally high red cell count
| - corresponds w/ increased hemoglobin levels
80
What is relative polycythemia?
- results from dehydration
- vomiting
- diarrhea
81
What is Gaisbock syndrome?
-stress polycythemia
82
What is polycythemia vera?
- Most common cause of primary ploycythemia
| - a myeloproliferative disorder leading to growth independent red cell progenitors
83
What gene is defective in polycythemia vera?
HIF-1a (hypoxia induced factor)
| a guy won a gold medal in skiing because of this
84
What are some common causes of excess bleeding?
- fragile vessels
- platelet deficiency or dysfunction
- deranged coagulation
85
What is prothrombin time (PT)?
- assess extrinsic and common coagulation pathways
- thromboblastin + Ca2+ = clotting
- prolonged PT = deficient Factors V, VII, X, prothrombin, and fibrinogen
86
What is the most common plasma cell dyscrasia of the elderly in the US?
MGUS
87
What is partial thromboblastin time (PTT)?
- assess intrinsic and common pathway
- kaolin + cephalin + Ca2+ = clotting
- Kaolin activates factor XII
- long PTT time = deficient factor V,VII,IX,X,XI,or XII
88
Do bleeding disorders with abnormal walls have normal or abnormal PT/PTT times?
normal
89
What Ehlers-Danlos syndrome Scurvy have in common?
- abnormal collagen = weak vessel wall = bleeding
| - purpura in the skin (also seen in cushings)
90
What is Henoch-Schonlein purpura?
- deposition of immune complexes on vessel wall
- purpuric rash, ab pain,
- acute glomerulonephritis
91
What is hereditary hemorrhagic telangiectasia AKA Weber-Osler-Rendu-Syndrome?
- autosomal dominant
- dialted tortous blood vessels
- mucosa bleeds = nose, tongue, mouth, eyes, GI tract
- TGF-B issue
92
What is perivascular amyloidosis?
- amyloid light chain (AL) amyloidosis
- mucocutaneous petechiae
- week blood vessels
93
A platlet count under ______ is likely to cause thrombocytopenia bleeding?
100,000 platelets/uL
94
Thrombocytopenia causes?
less platelet production
decreased platelet survival
sequestration
dilution (transfusions)
95
What is chronic immune thrombocytopenia (ITP)?
-antibody mediated destruction of platelets
may be secondary to lupus, HIV, B-cell
-primary is idiopathic?
96
What is the pathogenesis of chronic immune thrombocytopenia (ITP)?
-autoantibodies against platelet membrane proteins IIb-IIIa or Ib-IX
-antibodies are of IgG class
TX: splenectomy (red pulp is major site of opsonin destruction of platelets)
97
What are the clinical features of Chronic Immune Thrombocytopenia?
- Adult women 3:1
- young than 40
- insidiuous onset
- bleeding into skin and mucosa = bruising
- HX of easy bruising, nose bleeds, bloody gums, long menstral periods
98
How does ITP first present?
- usually with melena, hematuria, or excessive menstrual flow
- Subarachnoid hemorrhage may be leathal
- low platelet count
- large platelets in peripheral blood
- normal/increased megakaryocytes in marrow
99
What is a good Treatment for ITP?
- glucocorticoids (inhibit phagocyte function)
- splenectomy is severe cases
- anti-CD20 after splenectomy to treat relapse
100
What is Acute Thrombocytopenic Purpura?
- antibodies against platelets?
- kids
- 1-2 weeks after viral illness
- TX isnt usually needed
- TX in sever cases (20% of kids) glucocorticoids
101
What is heparin induced thrombocytopenia (HIT)?
-Type 1
instantly after TX starts
from platelet aggregating effect of heparin
-Type 2
less common. takes 5-14 days after TX
antibodies against heparin and platelet factor 4
STOP TX IMMEDIATELY
may lose limbs and get DVT and PE
102
What is HIV-Associated Thrombocytopenia?
- imparied platelet production & increased destruction
- one of the most common hematologic manifestations of HIV infection
- CD4 and CXCR4 on megakayrotcytes allows them to be infected by HIV which makes them prone to apoptosis
103
What are Thrombocytopenic Purpura (TTP) and Hemolytic uremic syndrome (HUS)?
- microangipathic hemolytic anemia and widespread organ dysfunction, and the attendant consumption of platelets leads to thrombocytopenia
- normal PT/PTT times
- thrombuc formation in tissues
104
What deficient plasma enzyme is TTP associated with?
-ADAMTS13 aka vWF metalloprotease
105
What is HUS associated with?
-normal ADAMTS13 levels
-infectious gastroenteritis be E. coli O157:H7
shiga like toxin
-atypical HUS
106
What marker is atypical HUS associated with?
- defect in complement factor H
| - CD46
107
Inherited disorders of platelet function can be classified into 3 pathogenically distinct groups:
1- defects in adhesions
2- defects of aggregation
3- disorders of platelet secretion
108
What is Bernard-Soulier Syndrome?
- defective adhesion of platelets to subendothelial matirx
| - defective Ib-IX
109
What is Glanzmann Thrombasthenia?
- Platelets fail to aggregate in response to ADP, collagen, epinepherine, or thrombin
- defective Ib-IIIa = no bridge formation
- bleeding = severe
110
Severe parenchymal disease leaves you at risk for what kind of bleeding?
Vit K, and factors II, VII, IX, X, and protein C are made in the liver so liver disease = defective coagulation
111
What is Von Willebrand Disease?
- the most common inherited bleeding disorder of humans
| - defects in platelet function inspite of normal counts
112
What are type 1 and type 3 von Willebrand disease associated with?
- quantantative effects
- Type 1 = autosomal dominant mild to moderate deficiency in vWF maturation or allows vWF to be quickly cleared from blood
- Type 3 = autosomal recessive, very low vWF = severe issue and is usually caused by deletions/mutations in both allels
113
Type 2 von Willebrand disease is characterized by ______
- qualitative defects in vWF
| - 2A is most common
114
What is hemophilia A?
- most common hereditary disease w/ life threatening bleeding caused by factor VIII mutations
- X-linked recessive
115
How does hemophilia A present clinically?
- brusing easily
- spontaneuos bleeds into joints
- ABSENT petechiae
- long PTT and normal PT
- TX: factor VIII infusions
116
What is hemphilia B (christmas disease. factor IX deficiency)?
- exactly like hemophilia A except instead of a broken factor VIII you have a broken factor IX
- x-linked reccesive trait
- long PTT, normal PT
- we diagnose hemophilia A and B with factor levels assay
- TX: IX factor infusions
117
What is Disseminated Intravascular Coagulation (DIC)?
-excessive activation of coagulation and the formation of thrombi in the microvasculature of the body
118
What is the pathogenesis of Disseminated Intravascular Coagulation (DIC)? and what are two triggers?
- DIC is NOT a primary disease
- 1- release of procoagulation factors into circulation
- 2- widespread injury to the endothelial cells (TNF released from this)
119
What are possible complications of DIC?
-widespread deposition of fibrin
leading to ischemia and microangiopathichemlytic anemia
-consumption of platelets
leading to hemorrhagic diathesis
120
Some conditions that may cause DIC are
```
pregnancy
massive trauma
surgery
severe burns
hypoxia
acidosis
shock
```
121
How does a patient with DIC present clinically?
- insidious, acute, chronic, fulminant
- 50% are obstetric patients
- 33% are carcinomatosous
- microangiopathic hemolytic anemia
122
How do you diagnose DIC? whats the prognosis?
-clinical observation ad lab studies for PT/PTT/fibrinogen levels
-prognosis: depends on te underlying cause
TX: remove underlying cause
123
What are hemolytic reactions to tranfusions?
-caused by preformed IgM antibodies against donor red blood cells that fix complement
124
What are delayed hemolytic reactions caused by?
- antibodies that racognize red cell antigens that the recipient was sensitized to previously
- i.e. through prior transfusion
- caused by IgG antibodies
- prove it with a + Coombs test
125
What is transfusion related acute lung injury (TRALI)?
- a severe, frequentaly fatal, complication
- transfused blood triggers the activation of neutrophils in the lung microvasculature
- MHC class 1 antigens who generate antibodies to MHC class 1 antigens expressed by the fetus
- more likely to occur after a transfusion or prior pregnancy
126
What do you see clinically with TRALI?
- bilateral pulmonary infiltrates that DONT respond to diuretics
- fever, hypotension, hypoxemia
- uncomplicated cases die 5% of time
- ill complicated patients die 67% of time
127
What is the treatment for TRALI?
-keep multiparous women from plasma donation has cut the incidence of TRALI in half
128
Why do stored platelets favor bacterial growth far more the stored red blood cells?
-platelets are stored at room temperature while RBCs stored colder
129
What do you do if a patient shows symptoms of fever, chills, and hypotension (this resemble non-hemolytic and hemolytic transfusion reactions)?
-start them on broad spectrum antibiotics while awaiting the lab results to specifically see what infection they have
