Hematology 2

Front 1

From what and where are platelets made?

Back 1

Platelets are normally made in the bone marrow from progenitor cells known as megakaryocytes

Front 2

What is the lifespan of a platelet?

Back 2

10 days (1/10 is replenished every day)

Front 3

What is the normal platelet count?

Back 3

150-450 x 10^9/l

Front 4

What is the basic platelet response?

Back 4

Platelets adhere to vessel wall, then aggregate, leading to formation of a platelet plug.

Platelets provide phospholipid scaffold for thrombin generation

Front 5

How many granules does platelets have and what do they contain?

Back 5

-granules: fibrinogen, von Willebrand f., fibronectin, f. V, PLT f. 4, -thromboglobulin, thrombospondin, PDGF


dense granules: serotonin, calcium, ADP, ATP

Front 6

platelet surface receptors?

Back 6

Gp1b: receptor for vWf
Gp2b-3a: Receptor for fibrinogen, fibronectin, vitronectin.

Front 7

Thrombocytopenia ''starts'' at:

Back 7

Usually lower than 130 x10^9/l (definition: below 100)
Severe: below 20 x 10^9/L

Front 8

Congenital (rare) throbocytopenia:
(acquired is more common)

Back 8

Fanconi´s s., Wiskott-Aldrich´s s., May-Hegglin a., Bernard-Soulier´s s., amegakaryocytic trombocytopenia. Often include thrombocytopathy

Front 9

Thrombocytopenia:5 broad categories of causes

Back 9

Pseudothrombocytopenia

Underproduction (AL, MDS, congenital TP, infiltration of bone marrow)

Peripheral Destruction or consumption (ITP, TTP, DIC)

Splenic sequestration (hypersplenism)

Other: dilution (multiple erytrocyte transfusions etc

Front 10

What is Pseudothrombocytopenia?

Back 10

Artificial platelet clumping in the tube with EDTA

Platelet clumping is of no clinical significance

Front 11

Thrombocytopenia due to Peripheral Destruction. 2 groups + sub gruops:

Back 11

Non-immune mechanisms:
Platelet activation and consumption:
e.g. TTP and DIC
Immune Mechanisms: ITP (immune trombocytopenia)
antibody-mediated platelet destruction
may be primary, secondary, or drug-induced.

Front 12

ITP – Immune Thrombocytopenia
(old name is idiopathic thrombocytopenic purpura)
Definition:
Etiology:
Incidence:

Back 12

Definition: isolated thrombocytopenia with no clinically apparent associated conditions or other causes of thrombocytopenia.
Etiology: autoantibodies directed against platelets coat platelet surface. IgG-coated platelets are taken up by RE system.
Incidence: approximately 100 per million; half of these are children. In adults, two peaks:
one are young (<40) with female predominance,
one are older (>60), no gender predominance

Front 13

How amny have autoantibodies in ITP? Anti what?

Back 13

75%
Anti-Gp on platelet surface.

Front 14

ITP definition:

Back 14

ITP = increased PLT destruction and suboptimal PLT production.


isolated thrombocytopenia with no clinically apparent associated conditions or other causes of thrombocytopenia.

Front 15

Role of lymphocytes in pathogenesis of ITP?

Back 15

Cytokine profile TH1/Th0 corelates with disease activity

Regulatory T cells reduced + not functional

T cells can directly influence MGKCs and decrease PLT production

25% ITP without detected antibodies: „T cell - mediated toxicity“

Front 16

B lymfocytes in ITP?

Back 16

Autoantibodies production

BAFF (B cell activating factor): TNF family

- Produced and released by monocytes a T lymphocytes

- increases lifespan of B and T lymphocytes decreases apoptosis

- BAFF itself increases apoptosis in thrombocytes
- mRNA BAFF in ITP patients s ITP is increased

Front 17

ITP - Diagnosis

Back 17

ITP is a Diagnosis of Exclusion (diagnosis per exclusionem)
No specific laboratory test can confirm diagnosis of the ITP
Need to exclude other causes of thrombocytopenia

Front 18

Which one is more common in primary/secondary ITP?

Back 18

Primary ITP. 80%
most common of the secondary ITP are SLE 5% and CLL 2%.

Front 19

Evaluation of Patient with Low Platelets: history

Back 19

History
Has the patient ever had a normal platelet count? Family history
Carefully review medications, including Over the counter meds.
Antibiotics, quinine, anti-seizure medications
Ask about other conditions which may be associated with low platelets
Liver Disease/hepatitis
Thyroid Disease - both hypo- and hyper-
Infections: viral, rickettsial
Pregnancy
Consider other conditions which may be associated with ITP
Lupus erythematosus, CLL, lymphoma, antiphospholipid syndrome

Front 20

Evaluation of Patient with Low Platelets: physical

Back 20

Physical
Evaluate for lymphadenopathy and splenomegaly
Look for signs of bleeding
Blood blisters and oral petechiae, ie “Wet Purpura”
best harbinger of intracranial hemorrhage

Front 21

Evaluation of Patient with Low Platelets: Laboratory data.

Back 21

Laboratory Data
Other blood counts should be normal.
Check B12 and folate levels.
Look at peripheral blood smear to exclude pseudothrombocytopenia, exclude TTP (especially if anemia also present.)
Send coagulation screens (PT/PTT) to exclude DIC
Send HIV, hepatitis serologies and TSH
H. pylori: antigen in stools or breath urease test

Front 22

Thrombocytopenia- when do you see symptoms?
When is it life threatining?

Back 22

100,000 - 50,000: no symptoms
No treatment generally required.
50,000 - 20,000: first symptoms
Generally need to begin therapy

20,000-10,000: may be life-threatening
Sometimes requires admission
<10,000: risk for spontaneous intracranial hemorrhage, usually requires inpatient treatment

Front 23

in asymptomatic adult with ITP If platelet count is >40-50 x109/l

Back 23

no therapy is required. Check platelet counts at designated intervals.

Stop all NSAIDS and ASA to improve platelet function

Front 24

If platelet count is < 20-30 x109/l in adult asymptomatic pat with ITP:

Back 24

If platelet count is < 20-30 x109/l , begin therapy with corticosteroids

Front 25

What corticosteroids are used to treat ITP and when?

Back 25

If platelet count is < 20-30 x109/l , begin therapy with corticosteroids. Or if symptomatic.
1. Prednison or
2. Methylprednisolone or
3. Dexamethason

NO corticosteriods in first trimester of pregnancy!!

Along with prednisone, add Calcium and Vitamin D to prevent bone loss

Front 26

After steroid treatment of ITP, how many will go into remission and how many apt will relapse?

Back 26

1/3 of adults will go into remission.
2/3 of patients will relapse during or after steroid taper.

Front 27

Management of Relapsed ITP

Back 27

Once the patient relapses, may need to use steroids to increase the platelet count out of the danger range, but THIS CANNOT SUBSTITUTE FOR DEFINITIVE THERAPY.
Prednisone is now a crutch to support a dangerously low platelet count. Long corticosteroid treatment should be avoided.
Options today include:
splenectomy, if contraindicated (including patient´s refusal):
TPO mimetics


In the past: intermittent treatment with anti-D immune globulin. (Patient must be Rh positive.
Not effective after splenectomy) NOT MORE AVAILIBLE DUE TO FATAL HEMOLYTIC ANEMIA)

Front 28

Management of Relapsed ITP, Splenectomy is usefull in how many cases?

Back 28

Splenectomy is effective in 2/3 of patients, leading to normal platelet counts.

Front 29

What does epistaxis mean?

Back 29

To bleed from the nose

Front 30

What is Evan´s syndrome?

Back 30

Immune trombocytopenia (ITP) + Autoimmune hemolytic anemia (AIHA)

Front 31

Heparin-Induced Thrombocytopenia (HIT). How often? When is it more common?
Which heparin?
What is the cause? What can it lead to?

Back 31

Seen in 1-3% of patients treated with heparin
Usually, 7-10 d after heparin started, platelets fall by at least 1/3 to 1/2.

Less often but still risk exists with low molecular weight heparin
More common in patients with vascular disease

Caused by antibodies against the complex of heparin and PF4. These antibodies activate platelets.
Can lead, paradoxically, to THROMBOSIS, in up to half of patients.

Front 32

HIT/T treatment

Back 32

IF PLATELETS FALL ON HEPARIN, STOP HEPARIN IMMEDIATELY.
Stop heparin
Stop heparin
Use a different anticoagulant
1. Fondaparinux (Arixtra®)

Front 33

What does cefalea mean?

Back 33

Migrane

Front 34

Microangiopathic Hemolytic Anemia (MAHA) (form of TTP)
Symptoms?

Back 34

Elevated LDH, elevated bilirubin
Schistocytes (fragmented RBC) on the peripheral smear
MUST BE PRESENT
Low platelets - MUST BE PRESENT
Fever

Neurologic Manifestations

Front 35

What is a Schistocyte?

Back 35

A fragmented erythrocyte.
Seen in eg. Trombotic thrombocytopenic purpura.

Front 36

TTP (trombotic trombocytopenic purpura)
Fatality?
Tretment?
What is contra indicated? Why?

Back 36

95% fatal prior to therapy, now 5% fatal.
Treatment relies on PLASMA EXCHANGE + corticosteroids


Platelet transfusions contra-indicated.
Multiple case reports of stroke and/or death during or immediately after platelet transfusion.

Front 37

HUS - Hemolytic Uremic Syndrome
How is it often classified? But how does it differ?

Back 37

Usually classified along with TTP as “TTP/HUS”


Has fewer neurologic sequelae, more renal manifestations.


More abdominal pain in symptoms
Usually precipitated by diarrheal illness, especially E. coli O157:H7 („Shigatoxin“) or Shigella

Front 38

To which category does ITP, HIT and TTP, TTP/HUS belong to?

Back 38

Thrombocytopenias

Front 39

Are thromocytopathies mostly inherited or acquried?

Back 39

Thrombocytopathies ar mostly Acquired

Front 40

Bernard – Soulier´s syndrome
What is it?
How to get it?
Cause?
Clinical?
Treatment?

Back 40

Congenital/inherited thrombocytopathy
AR inehritance

GP Ib/IX defect von Willebrand´s factor not bound adhesivity defective
Clinically: bleeding of „platelet type“, may be dengerous and fatal
Treatment is symptomatic

Front 41

Glanzman´s thrombasthenia
What is it?
How to get it?
Cause?
Clinical?
Treatment?

Back 41

Congenital/inherited thrombocytopathy
AR inheritance
Defect ib GPIIb/IIIa fibrinogen not bound
aggregation defective
Clinically: no spontenous bleeding but after invasion: surgery, dental, delivery, etc.

Th: symptomatic + rFVIIa

Front 42

Chediak-Higashi´s sy, Wiskott-Aldrich´s sy, Hermansky-Pudlak´s sy, Aspirine-like disease
Are example of what type of diseases?

Back 42

PLT secretory dysfunction

Front 43

Acquired thrombocytopathy
Give example of diseases ass. with it. (5)

Back 43

Myeloprolipherative diseases

Renal insufficiency
Liver failure
Autoimmune diseases
Myelodysplastic syndrome

Front 44

Medication-related thrombocytopathy with archacidonic acid involved. (3)

Back 44

Aspitin, corticosteriods, NSAID.

Front 45

Medication-related thrombocytopathy with plt cAMP involved?(3)

Back 45

Increase cAMP:
dipyridamol, theofylin, phospohodiesterase inhibitors,

Front 46

How doees clopidogrel work? And why is it related to on this topic?

Back 46

Clopidogrel: ADP receptor blocade --> GPIIb/IIIa inactivation --> LESS aggregation

Front 47

What is Thrombocytosis?

Back 47

PLT > 450 x109/l

Front 48

What Two major types of thromocytosis is there? + example of them.
Treatment when?

Back 48

1. Clonal thrombocytosis = ET (essential thrombocythaemia, PMF, PV, CML)

2. Reactive thrombocytosis: (eg. bacterial infection: osteomyelitis, iron defic, pneumonia, postsplenectomy.

Th: if >700 x109/l consider antiaggregation