Lecture class-

A chronic bleeding disorder—

Power point slide 1


Patient’s diary— (http://www.itppeople.com/joany.htm)

It all started in the summer of… when I returned from a long weekend … it was cool and rainy there.

I ate too many gravy coated potato fries, drove home in damp clothes, and caught what I thought was the flu.

Power point slide 2

It didn’t respond to my usual cure of lying on the sofa and watching four rented videos.


In a few weeks I noticed some black and blue marks on my arm and panicked when I didn’t stop bleeding from a small cut.


My days became a struggle to continue life, as I once knew it and understand why my body was betraying me.

As the slides are self-explanatory narratives, the lecturer is silent while displaying them but after letting them go through the slides and their books for 5-10 minutes the lecturer interjects a query:

What are the mechanisms for preventing spontaneous bleeds or normal quick cessation of any bleed?

At the end of the five-minute gap for the student to find out the answer from his/her information resource the microphone is passed around either in a linear or random sequence and students are encouraged to verbalize their thoughts.
After 3-4 responses the next power point projects the possible best response.

Power point slide 3


Physiology of Hemostasis

The cessation of bleeding from damaged blood vessel. 
After vessel injury, process of hemostasis takes place in 2 phases:
Primary:
1. Vessel wall contraction
2.Platelet aggregation & plugging of injured area
Secondary:
3. Formation of an insoluble fibrin clot due to activation of clotting system
In addition, there is a fibrinolytic system, which actively removes the clot

Lecturer interjects:

What are the abnormalities of hemostasis that may have caused abnormal bleeding in this patient?

Power point slide 4

Haemorrhagic diseases

Can result from abnormalities of:
 
Blood vessels
Platelets
Clotting systems

Lecturer interjects:

Diseases affecting the smaller blood vessels & platelets produce the clinical picture of purpura.

Clinical differences in variety of skin bleeds: Petechiae, Purpura, Ecchymosis—based on size of the bleed—Petechiae-1-2 mm, Purpura-<or =5mm, Ecchymosis>5 mm (See Clinical Image)

As this patient’s discussion is going to evolve around thrombocytopenia there is another slide on clotting disorder mentioned in passing (a separate class is generally required to discuss any of them in detail)

Power point Slide 5
Diseases of clotting system

Congenital      (Hemophilia, von-Willebrand’s disease)

Acquired   Deficiency of Vitamin K dependent clotting factors - severe liver disease, anticoagulant therapy; Hypofibrinogenemia –DIC, destruction of liver


Power point Slide 6

Patient’s diary— (http://www.itppeople.com/joany.htm)

After a short stint in the hospital for tests, the diagnosis was confirmed…


The hematologist wrote it down so I could remember what it stood for.


My count was 6,000, a severe case, potentially fatal. I didn’t know what a platelet was.

Lecturer interjects: What could be the possible reasons for a low platelet count in this patient?

Power point Slide 7

Thrombocytopenia

Causes

Impaired production:
Marrow aplasia,
Leukemia
Infiltration
Megaloblastic anemia
Myeloma
Myelofibrosis
Excessive destruction:
ITP,
Secondary Immune: SLE, CLL, viruses, Drugs e.g. Heparin
Sequestration:
Hypersplenism
Dilutional
Massive transfusion
Other:
DIC
TTP

Power point Slide 8

Idiopathic thrombocytopenic purpura                                                           (ITP)

Immune destruction of platelets
May occur following a respiratory or gastrointestinal viral infection
Usually a diagnosis of exclusion





Power point Slide 8


lMajor Bleed includes:
-  Intracranial Bleed
-  GI Bleed
-  Hematuria

-Minor Bleed includes:
-  Skin rash
-  Gum Bleed
-  Epistaxis
-  Menorrhagia

Power point Slide 9

Investigations

-CBC : Decreased platelet count
-P.Smear: -do-
-Prolonged BT ; normal CT
-Bone marrow : Increased megakaryocytes; rest-N,Vit-B12 , Folic Acid
-LFT, RFT
-Microbiology: Blood C&S
-Virology, Platelet Antibodies

Power point Slide 10


Treatment of chronic ITP in adults (http://www.emedicine.com/MED/topic987.htm#section~treatment)

Most physicians elect to not treat patients

Unless their platelet count is below 50,000/L

Or bleeding manifestations are present.


Power point slide 11

Only 15-25% of patients on steroids are expected to have lasting remission;

The remainder have disease characterized by frequent relapses and remissions


Power point Slide 12



Patient’s diary— (http://www.itppeople.com/joany.htm)


The hematologist suggested prednisone, the drug of choice. I was wary of the side effects, but this seemed to be the best option.

For three weeks I endured the brain fog, sleepless nights, and anxiety, hoping the drug would be a quick fix. It wasn’t.


There was only a slight rise in my platelet count, then a fall. He then suggested IVIg.

Power point Slide 13

(The slide data during actual class used only the headings for what has been detailed below) 


Intravenous immunoglobulin G (IgG) (0.8-1 g/kg for 2 d) results in a prompt rise in the platelet count, and this response confirms the diagnosis.

The mechanisms of action of intravenous gamma globulins are not clear.

Suggested mechanisms include blocking the macrophage Fc receptors, suppressing auto antibody production by providing antiidiotypes, and stimulating the clearance of auto antibodies.

The adverse effects of IgG include fever, nausea, vomiting, and, occasionally, renal failure. (http://www.emedicine.com/MED/topic987.htm#section~treatment)

Power point Slide 14


Patient’s diary— (http://www.itppeople.com/joany.htm)

As I was reducing the quantity of prednisone and had my first iv Ig treatment my body began to reel.

After a walk my blood pressure rose to an alarming level and I had chest pains.



The next day I collapsed and had a seizure.

Power point Slide 15


In the many hours of the day that I lay prone, I tried to counteract the stupor of the seizure meds by doing crossword puzzles and to think about my ITP and solve that puzzle too.


My platelet count slowly went down.

The next round of IVIg was less successful in raising my counts.

The round after that had almost no effect.

Power point Slide 16


Unlike in children, IVIG does not induce an early rise in platelet counts in adults and does not have an advantage over steroids as an initial therapy.

Second line therapies:

Elective Splenectomy : Chronic ITP patients who fail to maintain normal platelet count after a course of prednisolone are eligible for it

Power point Slide 17

Patient’s diary— (http://www.itppeople.com/joany.htm)

I agreed to have my spleen removed, hoping again for a quick fix and to put an end to the endless round of doctor appointments, hospitalizations and the constant fear of bumping my head and dying.



Before I left for the hospital I placed my will on my dresser.

Power point Slide 18

Splenectomy is effective because it removes the major site of destruction and the major source of antiplatelet antibody synthesis.

Before splenectomy, patients should receive a pneumococcal vaccine.

Even if complete remission is not achieved, the platelet count will be higher after splenectomy

Power point Slide 19


Patient’s diary— (http://www.itppeople.com/joany.htm)

My surgery was successful in that I survived, my spleen was removed and the wound eventually healed.


However, it was not successful in raising my platelet count.

Power point Slide 20

Approximately 10-20% of patients who undergo splenectomy remain thrombocytopenic and continue to have a bleeding risk that requires continued treatment.


Both steroid therapy and splenectomy are considered failures in these patients, and the patients are challenging to treat.

Power point Slide 21

Patient’s diary— (http://www.itppeople.com/joany.htm)


Three weeks after the surgery I had as few platelets as before the operation.

Now I was without a spleen, bruised, and still on the seizure meds.


It was now festival time and my family and I wondered if it would be our last together.

Power point Slide 22

A number of treatments have been proposed for splenectomy and steroid failures.

 Most of them are not based on placebo-controlled studies, and evaluating the efficacy of these treatments in a disease associated with spontaneous remissions and relapse is difficult.

Power point Slide 23

Other treatment regimes:

* High dose corticosteroids (iv)
High dose iv Ig
Rituximab
iv Anti-RhD
Danazol, colchicine
Vinca alkaloids
Immunosuppresive drugs: Azathioprine, Cyclosporine, Dapsone

Power point Slide 24

Patient’s diary— (http://www.itppeople.com/joany.htm)


My hematologist recommended Danazol…No luck…Colchicine failed too.

We even tried another course of IVIg hoping that my body would respond to it differently now that I didn’t have a spleen.

It responded differently all right. I was hospitalized following one of the treatments for a nosebleed that didn’t stop.

Power point Slide 25

I went to an ITP specialist in …and he berated my local hematologist for not putting me in the hospital.

I reluctantly agreed to a course of vincristine (chemotherapy) followed by a series of Prosorba A blood cleansing treatments.

They sneaked in more of the dreaded prednisone.


At the same time I also took up alternative wellness techniques that gradually began to enrich my life to the fullest.

I returned to work at the end of March, part time, wearing a wig, on the day that my short-term disability insurance ended.

My counts were still low, but I was thrilled to have parts of my life back. In a few weeks, I began full time work again.

Lecturer summarizes: This was an attempt to share a clinical scenario that has been posted by a real patient voluntarily on the net and who is presently doing very well with her platelets in the normal range as communicated to us on email. She is actively involved in helping others with bleeding disorders and is the founder President of
Platelet Disorder Support Association, 133 Rollins Ave., Suite 5,Rockville, MD 20852 www.pdsa.org
After going through her story and knowing more about the disease it may strike us that medicine is yet to reach an ideal state where everything would be perfect. However it does encourage us to gather more evidence, know more people like Joan and plan further research to address the issues this disease raises.