Dr. Singh - Hematopathology : RBC And Bleeding Disorders Flashcards
1
Q
How to access for anemia
A
You look at Hemoglobin (12-16) or you look at Hematocrit (36%-48%)
For women ranges
2
Q
How to measure the properties of RBCs
A
MCV(mean corpuscular volume) = Hct/RBC
MCH = Hgb/RBC
MCHC = Hgb/Hct
3
Q
Low MCV
A
Microcytic Anemia
Volume of each cell is smaller
4
Q
high MCV
A
Macrocyclic anemia
Volume of each RBC is larger
5
Q
Low MCH
A
Hypochromic (lighter in color in middle is larger)
Low amounts of hemoglobin in each RBC
6
Q
Polychromatic cells
What are they and how to confirm
A
They are Reticulocyte with a small RNA in them, they look more purple in color and slightly bigger then the RBCs
- confirm with supravital stain that stains the RNA inside it
7
Q
Normal or low Reticulocytes seen and anemia
A
The BM has a problem and does not make more RBCs, RBCs have low Hcrit and Hgb
8
Q
Anemia with many reticulocytes seen
A
There is a problem in the periphery causing the RBCs to not survive or function
BM produces more RBCs
9
Q
Anisocytosis
A
Elevated RDW (distribution of size in RBCs) **** FE+3 deficiency anemia**** can cause this
10
Q
Acute Blood Loss causes what to happen immediately and overtime
A
No difference in MHV and all other properties
- BP down, pulse up
OVERTIME :
- blood left pulls fluid from body = Hct and Hgb goes down (6-7hr later)
11
Q
Chronic Blood loss
A
Very mild and gradual sx
- pt can come in with 5.5 hgb and feel fine due to body compensation
EX: heavy menstrual cycle, GI bleeds
12
Q
Hemolytic Anemias what is it generally and 7 types
A
Peripheral destruction = high BM production of reticulocytes 1. G6PD deficiency 2. Hereditary Spherocytosis 3. Hemolytic anemia from trauma 4. Immunohemolytic anemia 5. Paroxysmal Npcturnal Hemoglobinuria 6. Sickle Cell 7. Thalassemia
13
Q
Hereditary spherocytosis is what
A
Inherited mutation in RBC cytoskeleton spectrin
Small pieces on the plasma membrane bud off over time and makes the RBC small and round (small dark cell)
= high risk of hemolysis
14
Q
Hereditary spherocytosis causes hemolytic anemia how
A
They are inflexible and unable to bend trough the vessels + MAINLY the spleen M eat them
= splenomegally + hypersplenism (many M made)
15
Q
Hereditary spherocytosis TX
A
Take the spleen out
16
Q
Hereditary spherocytosis on blood smear
A
Round and dark with no central pallor
Have Howell Jolly bodies if spleen is removed (DNA inclusions that the spleen normal removes) = a dot that is dark and small the RBCs
17
Q
Hereditary spherocytosis SX
A
Anemia (normal MCH, high MCHC, low MCV)
Jaundice
Splenomegaly
Can be mild
18
Q
Hereditary spherocytosis what can be life threatening
A
A Parvovirus B19 which attached Proerythrooblasts can cause an aplastic crisis, with extremely low RBCs extremely anemic
19
Q
G6PD deficiency is transmitted how and in what populations usually
A
X- linked + homozygous carriers can have SXs
Sub-Saharan Africa
Mid East
Mediterranean
20
Q
G6PD deficiency is what
A
G6PD makes NADPH which gives its electrons to make GSH (glutathione which is important to reduce free radicals)
21
Q
G6PD deficiency causes hemolytic anemia how and when
A
When the conditions in body makes a lot of free radicals (a few days after, not immediately after:
- Stress
- Drugs (anti-malaria….)**
- Foods like favs beans (favism)
- Infections
22
Q
Heinz bodies
A
Oxidative damaged proteins in the cells that climb together
Chopped out by the spleen
23
Q
G6PD deficiency is found in the aftercare Middle East and Mediterranean for what reason
A
Protects them from Plasmodium falciparum infection
24
Q
Sickle Cell Anemia is caused how
A
They have a B-chain mutation = HgS (normal HgA + HgB)
Mutation is GAG ——> GTG (Glu—> Val)
25
Sickle Cell Anemia Ss and SS and Ss
Heterozygous = SC trait
Homozygous SS = SC disease/anemia
Homozygous Ss = no SC
26
The populations that have a high chance of having Sickle Cell Anemia (HgS) can also be found to have what other hemoglobin modifications
1. HgbC
| 2. B-thalassemia
27
Sickle Cell Anemia have RBCs that prefer and especially under what conditions
Polymerization
- Hypoxia
- ICF dehydration
- Low pH = low O2 affinity
- sluggy blood
28
Sickle Cell Anemia polymerization can cause what to happen
The polymerizartion causes hemolysis of the RBCs and that causes occlusion of small vessels causing more hypoxia in certain areas
29
Sickle Cell Anemia RBC 2 main properties
1. Dense long polymer inside
| 2. Sticky surface from membrane damage
30
Sickle Cell Anemia SX
1. Acute resp distress
2. Acute chest syndrome
3. Asymptomatic bone necrosis (marrow emboli can happen)
4. Infarction of spleen (severe infection from capsular bacteria)
31
SC disease has what kind of hemoglobin
| SS disease has what kind of hemoglobin
HgS + HgC = milder
| HgS only = Sickle Cell Anemia
32
SC disease does what tho RBC
NO polymerization, the HgC crystallizes instead
They look like misshaped blobby RBCs (poikilocytes) + cells with pallor around the edge no in the center(Target cells)
Same risks and complications as SS only less severe
33
Sickle Cell Anemia TX
1. Hydroxyurea : increase HgF
| 2. CRISPR gene editing
34
Thalassemia locations its found
Around Mediterranean Sea and some of Africa and Middle East
35
B- Thalassemia MAJOR what happens
The HgA aggregate and form clumps inside the RBCs (due to no normal HgB) + (hypochromic)
1. Spleen hemolysis = hemolytic anemia
2. Ineffective making of RBCs in BM = hemolysis in the BM (hypoproliferative)
3. High Erythropoietin = BM expands
36
HgA and HgB are made from how many genes
A : 2 chr having 2 alleles = 4
| B : 2 chr having 1 alleles = 2
37
B- Thalassemia is what
You can have 2HgA + 1 HgB = MINOR/ Trait
OR
2HgA + 0 HgB = MAJOR
38
Ineffective erythropoiesis can cause what to happen
1. BM expands
| 2. Increased FE is taken into body = Fe overload (hyperchromatosis)
39
B- Thalassemia MINOR what happens
```
Mild
Mycrocytic anemia (confused itch Fe deficient anemia)
```
40
Microcytic anemia from B- Thalassemia minor vs Fe deficiency
B-th Minor : high Ferritin, normal or high Fe levels, normal transferrin
Fe D: low ferritin, Transferrin, Fe levers
41
a- Thalassemia different types and severity
1. aaaa = normal
2. a*aaa= asymptomatic carrier
3. a*a*aa= asymptomatic a-thal minor (mild microcytic anemia)
4. a*a*a*a= HbH disease symptomatic and microcytic+hemolytic anemia, splenomegally)
5. a*a*a*a* = fetal hydrops no life
42
a- Thalassemia with HbH disease what happens
Only 1 normal a-globin ——> you get 4HbB tetramer = HbH
It has highh affinity for O2 and cant deliver properly
= anemia and splenomegaly
43
a- Thalassemia with all 4 a-globins gone causes
Fetal hydrops = Hb Bart’s disease
1. Rely on embryonic Hb that is BAD at delivering O2 = fetal hypoxia + anemia
2. heart try’s to compensate = edema and effusion
3. Liver and spleen try to compensate = enlarge
44
Paroxysmal Nocturnal Hemoglobinuria (PNH) happens how
RBC have CD55 + CD59 on membrane to —I complement
1. Mutation in the PIGA gene = no CD55/59
2. MAC complexes form on RBCs = blood urine
45
PNH is transferred how
Acquired on X-chr on hematopoietic stem cells so it effects all blood cells
= can lead to not just hemolytic anemia, however also WBCs involved can cause AML + MDS
46
PMS pt can also have
AML and MDS
47
PNH Sx
1. Wake up and have blood in urine since at night blood pH lowers and MAC form more easily
2. Thromboembolism (portal, cerebral, hepatic)
48
PNH TX
1. Eculizamab ——I C5–>C5a
| = prone to get Neisseria infection (esp Neisseria meningitis)
49
Immunohemolytic anemia can happen in what 3 ways
1. Idiopathic = autoimmune hemolytic anemia
WARM Ab
2. Idiopathic = Chronic hemaggulutinin disease
COLD Ab
3. Mismatched blood transfusion (hemolytic D of newborn)
50
Coombs test : indirect and direct
I : test Ab in plasma
| D : test Ag on RBCs
51
WARM hemolytic anemia
IgG : more active in hot temps
Bind to RBCs to opsonizing them in spleen or phagocytoced
- Autoimmune or drug related
52
COLD hemolytic anemia
IgM : stronger affinity at low temps
Usually on nose and fingertips (Raynaud phenomena)
IgM makes C3b opsonizing cells removed then by spleen and liver and BM
53
WARM Hemolytic Anemia looks like what on blood smear
Kinda like hereditary spherocytosis
Round dark small cells
(RBC have Ab damage and condenses the cell)
54
Hemolysis from RBC trauma
1. Mechanically : prosthetic heart valve (causes laser cells that look similar to SS)
2. Microangiopathic hemolytic anemia : DIC, TTP/HUS-> thrombosis
55
Megaloblastic anemia what is it
Big cells of blood cells of many types (large N)
- NO Folate or B12 effects DNA of RBCs and other cells
- increased erythropoietin makes BM to increase synthesis however cant due to DNA impairment = hypercellularity in BM, still low reticular count in periphery
56
Megaloblastic anemia looks like what under blood smear
1. Low Hb, low Hct,
| 2. High MCV macrocytic (when lymphocyte is not larger then the RBCs on the smear you know)
57
How does B12 help make DNA
B12+ Methyl THF ——> 5,10-methylene THF polyglutamate
58
Pernicious anemia is what
Autoimmune disorder attacking the parietal cells of the IF itself
- seen in older adults usually
- lymphocytes attacked
59
Stomach cells that you see with Precarious an
Goblet cells are seen which should only be in the intestines
You see an accumulation of lymphocytes below the mucosa
60
Megaloblastic anemia SX
1. Atrophic glossitis : on tongue removed papillae and easy infection (when B12)
2. Gait or balance issues —> spinal demyelination in posterior and later nerves, taste, smell and visual changes, dementia
3. Anemia
4. Gastric problem (if B12)
61
Pernicious anemia DX
1. Megaloblastic anemia
2. Low B12
3. IF Abs
4. HIGH Homocysteine + HIGH MM Co-A
62
Folate Deficiency happens how
1. Pregnancy —> Neural tube defects
2. Marrow hyperplasia
3. Methotrexate
4. X absorption = sprue
5. Infancy, poor diet, alcoholism
63
Folate Deficiency DX:
1. Megaloblastic anemia
2. Low red cell folate measured
3. HIGH Homocysteine
64
Fe deficiency anemia on blood smear
1. Microcytic
2 hypochromic : low Hb
3. Hypoproliferative (due to low Fe)
4. ANISOCYTOSIS
65
When Fe comes into body where does it go
1. Marrow : stored as ferritin OR put into HgB on RBCs
| 2. Blood : by binding to Transferrin which carries it to the marrow
66
Hepcidin does what
BLOCKS FERROPORTIN from bringing Fe into the blood from the mucosa cells that it was stored in = this Fe gets pooped out
67
What can mess with the role of Hepcidin
High inflammation in the gut ——> high levels of Hepcidin = low Fe absorption even when the body needs it
68
Fe deficiency anemia causes
1. Diet
2. X absorption = sprue
3. Increased requirements
4. Chronic Blood loss
69
Stages of Fe Deficiency anemia
1. Ferritin Fe stores in BM decrease
2. Ferritin Fe stores decrease even more and RBC start becoming hypochromic
3. Sx of Fe deficiency start, no Fe stores in BM, anemia
70
Fe Deficiency anemia SX
1. Koilonychia : fragile nails with vertical stripes
2. Alopecia : hair loss
3. Atrophic glossitis (like pernicious anemia)
4. Angular cheilitis (side of mouth skin is irritated and raw looking)
71
Fe study of Fe Deficiency anemia shows what
1. Low FE, ferritin, hepcidin
2. High TIBC (total iron binding capacity)
3. Marrow has less stained Fe
72
What can look like Fe Deficiency anemia
```
Anemia of chronic disease :
1. Inflammation (immune disease, pernicious anemia)
2. Malignancy
3. Infection
= THEY HORDE FE (won’t let them go)
```
73
Reason anemia of chronic disease take Fe and does not give it
1. Cytokines = hepcidin increases
| 2. Erythropoietin decreases for some reason
74
What do you see in the anemia of chronic disease blood
1. Low Fe in serum
2. Low TIBC
3. High ferritin (not from high Fe only from inflammation)
4. A lot of Fe stained in the tissues in BM
75
Aplastic Anemia is what and what do you see in BM
Only fat almost
Panocytopenia (all cells are low)
thrombocytopenia
Anemia
76
Aplastic Anemia is caused usually because of what
1. Drugs (chemotherapy, adverse reaction to NSAIDS or AB)
2. Irradiation
3. Viral infection
4. Rare inherited Fanconi anemia (DNA repair defect, new stem cells destroyed by body, or new stem cells cant make right blood cells)
77
Aplastic Anemia SX
1. Bruising
2. Anemic -> fatigue
3. Febrile (low Granulosites)
4. Leukopenia
78
Aplastic Anemia BLOOD SMEAR
Normocytic + LIKE NO reticulocytes
79
Aplastic Anemia DX how
Go to BM and see to rule out any other disorder (you should see mostly fat, no cells)
80
Pure red cell aplasia happens when
1. Autoimmune problem (usually thymoma) —> Myasthenia gravis
| 2. Parvovirus B19 infection (especially when the patient has hemolytic anemia)
81
Myelophthisic anemia is what
Something is taking up space in the BM , preventing blood cells from maturing and being made
1. Cancer (neuroblastoma)
2. Necrosis
3. Fibrosis
4. Inflammation
82
Myelophthisic anemia causes what and what do you see on the blood smear
Very abnormal cells if they manage to escape from the BM = LEUKOERYTHROBLASTOSIS : immature erythroid and myeloid cells
1. Blast forms
2. Early precursor cells
3. Hypechromatic RBCs
4. Abnormal shaped cells
83
Stages of fixing a vascular injury
1. Vasoconstriction : to direct blood away from the injury
2. Platelet plug
3. Coagulation cascade and stabilize plug
4. Fibrolysis
84
Primary disorder is caused by what and what are the common SX
Platelets dysfunction (vWF), vessel wall disfunction
- skin and superficial bleeding
- petechiae and eccymoses
- immediate bleeding
- Autosomal D = not as serious
85
Secondary disorder is caused by what and what are the common SX
Coagulation disorder
- deep bleeds in muscles and joints and tissues
- Hematomas, hemarthroses (F8 deficiency)
- Delayed bleeding
- AR or X-linked - more serious
86
Tertiary disorder is caused by what and what are the common SX
Fibronolysis factors are elevated
- wounds and GI/GU tract bleeding
- delayed bleeding
- hematuria an menorrhagia
- autosomal recessive
87
How to see wall abnormalities
You have to look at History and PE
88
How to see reduced platelets
CBC
89
How to see function of platelets
Platelet function test, morphology
90
How to see clotting factor abnormalities
PTT and PT
91
Vessel wall disorders can happen from
1. Aging : more fragile BVs
2. Infections
3. Ehlers Danlos
4. Scurvy
5. Cushing syndrome (high corticosteroids) or other steroids
6. Hereditary Hemorrhagic telangiectasia (skin and GI mucosal bleeding)
7. Perivascular amyloid : can happen in myeloma (periorbital bruising, raccoon eye from amyloid deposition)
92
Thrombocytopenia
Low platelets that can be very low (below 150,000) and still have no sx
When it reaches 50,000 you see sx
At 20,000 you have spontaneous dangerous bleeds
93
HIV - associated thrombocytopenia
1. Infection goes to BM and it’s hematopoietic stem cells = no platelet production
2. Auto-Ab against Platelets made
94
Drug induced thrombocytopenia
1. Myelosuppression : chemo, chloramphenicol, Penicillamine , Gold salts (for aplastic anemia) = no P made
2. Drug- induced immune thrombocytopenia : Quinidine, Vancomycin, Heparin = destroy P in periphery by drug induced Abs
95
Heparin and drug induced thrombocytopenia
Heparin binds to the PF4 complex which then binds to platelets
This causes IgG to come and opsonizing it
- thrombocytopenia + thrombosis
96
Immune thrombocytopenia purpura
Autoimmune problem where Ab coat platelets and they can destroyed in the spleen
- spontaneously (acute or chronic, chronic harder to tx)
- viral (Hep, HIV)
- SLE
97
Immune thrombocytopenia purpura SX
Petechiae and purpura
CBC = low platelets
Platelet Ab stain can be + or sometimes - : so best thing to do is look at BM and see INCREASED MEGAKARYOCYTES
98
Immune thrombocytopenia purpura TX
- corticosteroids
- IVIg
- Anti-CD20 ( Rituximab) -> attacks B-cells
99
Thrombotic microangiopathies : TTP/HUS
Non- immune destruction of platelets
1. Thrombotic thrombocytopenia
2. Hemolytic Uremic Syndrome
100
Thrombotic thrombocytopenia (TTP) SX
```
Fever
Thrombocytopenia
Microangiopathic hemolytic anemia
Neurological defects
Renal failure
=PENTAT ****
-more in adults
```
101
Hemolytic Uremic Syndrome (HUS) SX`
1. Same SX as TTP however more Kidney problems then brain problems
2. More in kids
102
TTP and HUS happens how
1. An exaggerated platelet plug forms and consumes all platelets
2. RBCs sheat and burst when they hit themselves against the platelet bumps in the vessels
103
TTP and HUS on Blood smear
You see
- no platelets
- some uncleared RBC due to mature RBCs getting sheared
- schistocytes : sheared RBCs
104
What exactly happens in TTP
The vWF and platelets make the platelets plug and the PROTEASE is what prevents the plug from growing too big
**** ADAMTS13 mutation on protease so body has Abs against it = X protease
= microvascular thrombosis
105
TTP TX
Plasma exchange therapy
| Exchange all plasma with new plasma what has no ADAMS13 mutation on the protease
106
HUS what exactly happens + initial SX
From the shiga- like toxin from E. Coli O157: H7
= bloody Diarrhea
* check if there is thrombocytopenia, Microangiopathic hemolytic anemia, and renal insufficiency = HUS TRIAD****
107
HUS TX
To infection and hydrate them
108
No platelet adhesion caused by
1. Bernard Soulier (Gp1b R)
| 2. vWF factor disease (vWF)
109
No aggregation of platelets
Glanszmann thrombocytopenia (Gp2b-3a)
110
No granule (ADP, thromboxane release) =
Storage pool disorders, Factor 5, vWF, ADP, thromboxane
111
Acquired platelets function problems
Uremic acid : platelets to tank (Uremia)
| Aspirin
112
Grey Platelet Syndrome is what
X a-granules in the platelets
| (They contain , Factor 5, vWF, fibrinogen)= bleeding, big and grey and no granules in platelets blood smear
113
vWF in secondary Hemostasis
vWF in circulation binds to F8 and carries it to the platelet plug and then it can convert F10 —> F10a
114
vWF D not enough of this
Type 1 and Type 3(worse has absolutely no vWF = coagulation and platelet disorder )
1C= makes it only it gets rapidly broken down and cleared
115
vWF D qualitative
```
Type 2 ( 2A no multimer forming)
Defected ligand factors
```
116
Hemophilia SX
Arthrphathy
Hemorrhage in retroperitoneaum or soft tissues
Muscle hematoma
117
Hemophilia A and B
| SX
```
A : F8
B : F9
- deep bleed after trauma
- isolated PTT
- X-linked
```
118
Hemophilia A and B TX
Replacement factor or F8 or F9
119
Plt : N
PT : N
PTT : HIGH
- X F11
- mild to moderate hemophilia A or B (injury bleeding)
- mild vWF (spontaneous bleeding)
- severe vWF, Hemo A/B (Severe spontaneous bleeding)
- heparin, lupus anticoagulant (no bleeding)
120
Plt : N
PT : High
PTT : N
X F7
121
Plt : N
PT : High
PTT : HIGH
1. X F2, F5, F10 (common pathway)
2. Afibrinogenemia
3. X F5+F8
122
Plt : LOW
PT : High
PTT : HIGH
DIC (Disseminated Intravascular coagulation)
| Liver disease
123
DIC (Disseminated Intravascular coagulation)
1. Thrombohemorrhagic disorder (too much spontaneous coagulation formation , thrombi)
2. Consumptive coagulation (bleeding, no coagulation lefts to fix it)
= widespread thrombosis all over in tiny vessels
124
DIC (Disseminated Intravascular coagulation) caused by
Too much tissue factor released
125
DIC (Disseminated Intravascular coagulation) SX
1. Consumption of all clotting factors
2. Ischemia tissue damage
3. Bleeding (X coagulation, + thrombosis activated plasmin = fibrinolysis)
126
DIC (Disseminated Intravascular coagulation) can cause what to happen
1. Black fingers and toes
| 2. Hemorrhage of the adrenal glands = Waterhouse- Friderichsen Syndrome
127
DIC (Disseminated Intravascular coagulation) DX
1. Low PLT
2. HIGH PT and PTT
3. HIGH D-dimes (product of plasmin lysine coagulation factors = fibrinolysis)
128
transfusion screens for what
1. Donor HEP, HIV
| 2. Blood tested for : HIV, HBV, West Nile, Zika, chagas, syphilis, hcv, htlv
129
How can a donors blood get infected
Sometimes especially platelets that are stored at room temperature can get infected by bacteria if contaminated in any way
= recipient gets hypotensive and febrile immediately during trasnfusion
130
Acute immune hemolytic reaction happens how and when
If mismatched blood type happens
| - by IgM antibodies
131
What does it mean o be A- or B- or AB-
You are Rh- and you have Anti- D Ab
| Rh+ has no Anti-D Ab
132
Delayed immune hemolytic reaction happens how and when
During transfusion or mixing of blood that is Rh+ and Rh-
= makes IgG, so the first time its exposed it is fine only the second time there will be hemolysis and problems
(ESP Rh- mom and Rh+ fetus)
133
2 types of delayed immune hemolytic reaction
1. Rh+ fetus and Rh- mom
2. IgA deficiency patient getting a blood transfusion
= uses IgG
134
IgA deficiency patient getting a blood transfusion what happens
The pt has Anti-IgA IgG-antibodies that attack any IgA that it gets from any transfusion
= anaphylactic reaction
= you need was the blood before giving it
135
Acute Lung Injury (TRALI)
Transfusion related
| = inflammation and infiltrates start to accumulate in the lungs of recipient (acute resp failure)
136
Acute Lung Injury (TRALI) SX
Difficulty breathing
Fever + Hypotension (mimicking sepsis)
= during or after transfusion
137
Immune modulation (TRIM)
Transfusion related
When a pt is being transfused :
1. Immune system is somewhat pro-infammatory state always
2. Immune system is also downregulated from pathogens and things happening in the body that actually need to be taken care of due to being distracted by the transfused entities
**** really make sure patient needs a transfusion, PROS over CONS
