Flashcards in Module 1: Clotting Deficiencies, Mono, Follicular and Hairy Cell Deck (44):
Idiopathic Thrombocytopenic Purpura is a clotting disorder, what is the pathogenesis for this disorder?
Immune: destruction of antibody coated platelets in the spleen
What is the treatment for children and adults in Idiopathic Thrombocytopenic Purpura?
Children: usually following viral URT and undergoes spontaneous resolution
Adults: need steroids or splenectomy
What is the presentation of idiopathic thrombocytopenic Purpura?
Petichae and Purpura
What do you find in the blood and bone marrow in patients with Idiopathic thrombocytopenic purpura?
Blood: Increased bleeding time (But PT and PT are normal), decreased platelets (thrombocytopenia), normal RBCs and WBCS (no anemia or neutropenia)
BM: increased megakaryocytes to compensate
What are the complications for idiopathic thrombocytopenic Purpura?
---self limited in children
--splenectomy in adults
What syndrome is seen in children 1 week after bloody diarrhea?
Hemolytic Uremic Syndrome (HUS)
--caused by enterohemorrhagic E. Coli --- abnormally cleaved vWF --- platelets mechanically cleave RBCs
In these children that develop hemolytic uremic syndrome, what symptoms do they develop?
1. Microangipathic hemolytic anemia
2. Thrombocytopenia (increased bleeding time leads to purpura)
3. Acute renal failure (intravascular hemolysis --free Hb ----ATN)
What do you see on blood smear for these children that develop hemolytic uremic syndrome?
Schistocytes or helmet cells
Large dark granules inside the neutrophils
Increased bleeding time
--schistocytes are also seen in patients with prosthetic valves (mechanical trauma to the red cells) -- decreased Hb, increased reticulocytes and increased total bilirubin and decreased heptoglobin
There are two main hereditary clotting factor deficiencies we will discuss on the notecards. The first is Von Willebrand Disease, what is this a defect in?
Most common bleeding disorder
---defect in platelet to collagen adhesion
There are different types of Von Willebrand disease. First explain type 1 and 3.
Type 1 &3: decreased quantity of VMF (Von Willebrand Factor)
Type 1: 70%; mild, mucosal bleeding
Type 3: severe deficiency/lack of VMF
--affects F-VIII stability in plasma
---patient may clinically present like hemophilia A
Now explain type 2 Von Willebrand disease
Type 2: qualitative/functional abnormality of VWF
affects 25% ; mild-moderate bleeding
The next hereditary clotting factor deficiency to discuss is Hemophilia A. What is the defect in this disease?
X-linked recessive: deficiency in factor VIII in the clotting cascade
what will the lab values in hemophilia A look like?
Normal Platelets, BT and PT
Patients with hemophilia A run the risk of massive bleeding after what?
Trauma or surgery
The next topic we are going to discuss is Infectious Mononucleosis. One of the etiologies of this infection is EBV, what is a list of diseases that are affected by EBV?
Hodgkin's Lymphoma (mixed cellularity and lymphocyte depleted)
Oral Hairy leukoplakia
What is the etiology for Infectious Mononucleosis (glandular fever)?
Epsten Barr Virus (EBV) (HHV4)
CMV (HHV5): this can also cause infectious mono disease but its not actually mono and symptoms are exactly the same
How is Mononucleosis transmitted?
Salivary Transmission (high school kids get this alot)
How does Mononucleosis present?
Sore throat (pharyngitis)
Lymphadenopathy (cervical, axillary, inguinal)
If a patient comes to your office and you miss diagnose then with strep instead of mono, what additional symptoms will the patient get?
Penicillin treatment will cause a generalized rash
What is the pathogenesis for Mononucleosis?
Infects B cells but reactive cells = T cells
What is the best diagnostic test for these patients?
1. Monospot/heterophile antibody best test
--positive for EBV and negative for CMV
2. Lymph node biopsy: again infects CD4 B lymphocytes but CD8 T cells respond because its a virus
--paracortex of lymph nodes is where T cells are kept
What will a peripheral blood smear of a patient with mononucleosis show?
Downey cells: CD8 T cells, atypical lymphocytes and reactive lymphocytes
What are the complications of Mononucleosis?
1. Splenic Rupture: splenomegaly --- peritonitis (Death) ---- hypovolemic shock
2. Non-Hogkin's B Cell Lymphoma (Burkitt's)
3. Cold Autoimmune hemolytic Anemia: IgM
What is the tx for mononucleosis, also what advice should you give a patient?
Tx: supportive care
Advice: Avoid contact sports to avoid spleen rupture
Now moving on to B cell lymphoma's. Follicular lymphoma is a common tumor that constitutes 40% of the adult Non-Hodgkin's Lymphomas in the US. What is the pathogenesis for these tumors?
---Neoplastic cells express BCL2 (protein that is absent from normal germinal center B cells)
-- 14;18 translocation b/w heavy chain that fuses the BCL2 gene on chromosome 18 to the IgH locus on chromosome 14
--this chromosomal rearrangement explains the overexpression of BCL2 protein in the tumor cells
What would a lymph node biopsy on a patient with follicular lymphoma show?
Lymph nodes are effaced by a nodular proliferation
--the tumor cells resemble germinal center B cells
--predominant neoplastic cells are larger than lymphocytes and have angular cleaved nuclei
What population do you find follicular lymphoma in?
Middle aged, 40-60
What is the most common location of follicular lymphoma/
2nd part of duodenum
--can compress head of pancreas/ampulla of Vater--- obstructive jaundice and back up of conjugated bilirubin --- dark urine, steatorrhea and malabsorption of fat soluble vitamins (A,D,E,K)
About 40% of follicular lymphoma transform to what?
To a more aggressive lymphoma (DLBL)
--can only survive 1 year after transformation
Follicular Lymphoma is a type of Lymphoid Neoplasm. What is a lymphoid neoplasm?
Classification is based on cell of origin stage of differentiation
-mass derived from germinal center B cells
The next lymphoma that will be discussed is considered a miscellaneous lymphoid neoplasm, Marginal Zone Lymphoma. What time of tumor is it and were does it arise?
Indolent B cell tumor arises most commonly in epithelial tissues such as stomach, salivary glands, small and large bowel, lungs, orbit and breast
Marginal Zone Lymphomas tend to develop in what situations?
Auto-immune disorder (Sjogren syndrome and Hashimoto thyroiditis)
Or chronic infection such as H.pylori gastritis
Where is the most common site for Marginal Zone Lymphomas?
Stomach (superimposed on H. gastritis)
--tx with abx to eradicate the organism leads to regression of the tumor cells
The next miscellaneous Lymphoid Neoplasm, that will be discussed is Hairy Cell Leukemia. What type of leukemia is it?
Indolent (Slow to develop) mature B cell neoplasm characterized by the presence of leukemic cells with fine, hairlike cytoplasmic projections
What population is affected by hairy cell leukemia?
Middle aged men
--gradual onset, takes awhile to present
What do patients present with who have hairy cell leukemia?
1. Pancytopenia: normocytic, normochronic anemia
---patients get fatigue and recurrent infections due to neutropenia and bleeding due to thrombocytopenia
2. Hepatosplenomegaly: infiltration of the hairy cell in the spleen and liver results in compensation ---Extramedullary Hematopoiesis (decreased hemopoietic cells) (hairy cells get caught in the red pulp sinusoids)
3. No lymphadenopathy (too small)
What do you see on bone marrow aspirate on a patient with hairy cell leukemia?
Bone Marrow Aspirate:
Dry tap: hairy cells secrete TGFbeta resulting in fibrosis
What do you see on Bone marrow biopsy on patients with hairy cell leukemia?
--initially hypercellular until fibrosis from TGFbeta builds up
--Fried egg appearance
--Reticulin stains collagen black in bone marrow
What do you see in flow cytometry for Hairy Cell Leukemia?
Most Accurate Diagnostic Test:
--CD25, 11c, and 103
What do you see on Peripheral Blood Smear on patients with Hairy Cell Leukemia?
Peripheral Blood Smear:
--Malignant B cells with fine cytoplasmic hairlike projection
--Positive TRAP stain (tartrate resistant acid phosphatase)
What are the complications of Hairy Cell Leukemia?
Recurrent Infections is the most common cause of death due to neutropenia
CHF due to anemia
What is the treatment for Hairy Cell Leukemia?
Splenectomy and Alpha-Interferon
Now, extremely sensitive to chemo, particularly purine nucleosides (over 75% survival at 12 years)
Review: What is the only leukemia that does not do pancytopenia?