Tests for platelet abnormalities

1. First do platelet count: if you took an aspirin you still have a normal # of platelets, but they don’t work.

2. Secondly do Bleeding time – assesses platelet function

3. Test for vWF? Ristocedin cofactor assay - if missing vWF, ristocedin can’t cause platelets to clump (most sensitive test for dx’ing vWF dz).

So, three tests that assess platelets: platelet count, bleeding time, ristocedin cofactor assay (for vWB Dz)

Example: older man with osteoarthritis – prostate was resection and massive bleeds: if have osteoarthritis, you have pain, and if you have pain, you will be on pain medication, an NSAIDS, and will give test results – PT/PTT/platelet count all normal – bleeding time is longer. Rx – platelet pack transfusion – when you give from a donor, it WILL work (donor’s platelets are normal). So, if your taking NSAIDs, platelets not working and if you have a prob during surgery, give pt platelets from donor.

Audio day 3: hematology file 7 F. Extrinsic vs. Intrinsic system:

1. Factors involved:

Extrinsic = factor 7

Intrinsic = factors 12, 11, 9, 8

Both share the same final common pathway – factor 10. (What is another system that has a final common pathway? Complement–whether by the classical pathway, the alternate pathway, or by the MAC pathway, all includes C3)

What do we have left? 10, 5, 2 (Prothrombin), 1 (fibrinogen) and then the clot.

2. Tests involved:

a) Prothrombin time (PT):

Evaluates the extrinsic system all the way down to the formation of a clot – so it only deals with 7, 10, 5, 2, and 1. End stage of the test is a clot in the test tube. INR = standardized way of doing it – standardization technique (same everywhere in world).

b) Partial thromboplastin time (PTT):

Evaluates the intrinsic system all the way down to a clot – so it deals with 12, 11, 9, 8, 10, 5, 2, and 1.

Example: PT is prolonged, but PTT is normal, what is the factor def? 7

B/c the prothrombin was prolonged; this includes 7, 10, 5, 2, or 1. And the PTT are normal, meaning that 12, 11, 9, 8, 10, 5, 2, 1 are all normal. So the only one responsible is 7.

Example PTT is prolonged, but PT is normal, what is the factor def? Factor 8 (play odds).

Why? If PTT is prolonged, it is 12, 11, 9, 8, 10, 5, 2, and 1 that is the problem. However the PT is normal, therefore 7, 10, 5, 2, and 1 are normal. Therefore, its one the PTT factors (12, 11, 9, 8). We know what hemophilia A (next to vWB Dz) is the MC factor def, therefore, if you play odds, it’s a factor 8 def.

Example: what did warfarin block? Epoxide reductase. So, that prevented the gamma carboxylation of Factors: 2, 7, 9, and 10. So, what do you follow with warfarin? PT.

What is the only factor you are not evaluating to when you are doing a PT time for a person on warfarin? Factor 9 – b/c its part of the intrinsic system. What is the PTT in a person on warfarin? Prolonged b/c factors 2 and 10 are vit K dependent factors in the final common pathway. However, PT does a better job in evaluating warfarin b/c 3 out of the 4 things that it’s involved in are in the prothrombin time. So, both PT and PTT are prolonged when you are on warfarin, but PT is better diagnostic tool.

Example: what do you follow heparin therapy with? PTT (evaluates the intrinsic

pathway). Factors that antithrombin III knocks off: 12, 11, 7, 10, 2, 1 are all neutralized by antithrombin III. So, with pt on heparin, PTT is prolonged, what is the PT?

Prolonged. It’s just that the PTT does a better job at evaluating heparin (many factors antithrombin III involved with)

So, BOTH PT and PTT are prolonged if on warfarin or heparin; however, it turns out that PTT is better at evaluating heparin and PT is better for warfarin.

II. Fibrinolytic system: Plasmin

Plasmin – leaves crumbs – its breaks down things (fibrinogen, fibrin, coagulation factors) – think fibrinoLYTIC system. When it breaks down a clot, there are many pieces (ie fibrin) left around, which are fibrin degradation products.

What is the single best screening test for DIC? D-dimers (better answer) or fibrin split products.

What plasmin does is breaks things apart, leaving crumbs behind and you have degradation products. D dimers are the absolute best test for DIC (di- means 2). When you form a fibrin clot, factor 13 (fibrin stabilizing factor) makes the clot stronger. How do you stabilize strands? Link them by putting connections between them to make them stronger (this is what factor 13 does). So, how do you make collagen stronger? By, linking them to increase the tensile strength (factor 13 will put a crossbridge in fibrin). What D-dimer is detecting are only those fibrin factors that have a link (ie when there are two of them held together, this what the test picks up). What does this absolutely prove? That there is a fibrin clot. Do you see this in DIC? Yes.

Example: Would you see it if you broke apart a platelet thrombus in a coronary artery? (Remember a platelet thrombus is a bunch of platelets held together by fibrin). So, what would the D dimer assay be if you broke apart that clot? Increased, you would see increased D dimers and would see the little fibrin strands held together by cross linking. They often do that to see if you have recanalized or if you got rid of your thrombus.

Example: it is often also seen with a pulmonary embolus, b/c if you have a pulmonary embolus, one test is a D dimer b/c you will form a clot that will activate the fibrinolytic system, and it will try to start breaking it down, and there will be a release of D dimers. Single best test for DIC. Good test for picking up pulmonary embolus, along with ventilation/perfusion scans. Excellent test to see if you have reperfusion after given t-PA b/c it proves that if D dimers were present, a fibrin clot must be present (fibrin was there so it proves it).

III. Vessel abnormalities

A. Senile purpura: Seen on the back of hands of an old person – they hit things and get senile purpura; vessels get unstable as you get older and subcutaneous tissue thins. When you hit yourself, BV’s rupture and you get echymoses – called senile purpura, an age dependent finding.

Only present in places that normally hit things, back of the hands and the shins. Example: Mom was put in old age home and the children were gonna sue the old age home for abuse. Do the children have a case? No, b/c it has nothing to do with abuse and is an age dependent finding.

Example: now if they also saw echymoses on buttocks and back, this is not a normal place to get trauma related to just bumping into things – that would be abuse. Senile purpura is the

cause of echymoses on the back of the elderly’s hand. Everyone will get this, everyone, no one is exempt.

B. Osler Weber Rendu Dz aka hereditary telangiectasias: Many of these pts have chronic Fe def anemia, related to persistent GI bleeds. You can make the dx with PE of the pt. The pt will have small red dots called telangiectasias and if you look on the lips and tongue you will see telangiectasias, and if you do endoscopy, you will see the little red dots throughout the GI tract.

What does this pt have? Osler Weber Rendu Dz aka hereditary telangiectasias. It is the MC genetic vascular dz. Therefore, you can see why you get chronic Fe def and bleeds b/c the telangiectasias will rupture. It is kind of like the angiodysplasia of the skin

So, these are the two vessel dz’s: senile purpura and Osler Weber Rendu dz, and also scurvy.

IV. Platelet Abnormalities

Findings of platelet problems: all have a problem in making a hemostatic plug, epistaxis (MC), petechia, echymoses, and bleeding from superficial scratches/cuts.

Example: 12 y/o kid, with URI one week ago, presents with epistaxis. Perform PE, and you see lesions that do NOT blanch (need to know the difference between petechia and spider angiomas:

petechias do not blanch b/c bleeding into the skin; spider angioma WILL blanch b/c it’s an AV fistula). Platelet count is 20,000. What is your dx? Idiopathic thrombocytopenic purpura.

Mechanism: IgG against the platelet. What type of HPY is this? Type II. Who is removing the platelet? Macrophages in the spleen (b/c IgG marked the platelet for destruction by the macrophage). This is similar to autoimmune hemolytic anemia, but this is autoimmune

THROMBOcytopenia. Rx – if they are very symptomatic, give corticosteroids; if not, leave alone and it will go away.

Example: woman with “+” spearman Ab test, epistaxis, petechia, generalized tender

lymphadenopathy, and splenomegaly. Pt has LUPUS, autoimmune thrombocytopenia, same mechanism: IgG auto-antibodies against platelets, a type II HPY rxn, with macrophage related removal.

A. TTP (thrombotic thrombocytopenic purpura) and HUS (hemolytic uremic syndrome)