Ed Friedlander, M.D., Pathologist

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

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Freely have you received, give freely With one of four large boxes of "Pathguy" replies.

I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.

Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.

I am presently adding clickable links to images in these notes. Let me know about good online sources in addition to these:

Also: -- my cyberfriends, great for current news and browsing for the general public

EnjoyPath -- a great resource for everyone, from beginning medical students to pathologists with years of experience
Medmark Pathology -- massive listing of pathology sites

Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures

Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of requests for information weekly, all as a public service.

Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

If you're a private individual who's enjoyed this site, and want to say, "Thank you, Ed!", then what I'd like best is a contribution to the Episcopalian home for abandoned, neglected, and abused kids in Nevada:

I've spent time there and they are good. Write "Thanks Ed" on your check.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.

During the eighteen years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and William Carey as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at William Carey for making it still possible, and my teaching assistants over the years.

Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!



More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
What is Cancer?
Cancer: Causes and Effects
Immune Injury
Other Immune
HIV infections
The Anti-Immunization Activists
Infancy and Childhood
Environmental Lung Disease
Violence, Accidents, Poisoning
Red Cells
White Cells
Oral Cavity
GI Tract
Pancreas (including Diabetes)
Adrenal and Thymus
Nervous System
Lab Profiling
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Serum Proteins
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Alternative Medicine (current)
Medical Dictionary

Courtesy of CancerWEB

{26443} platelets
{26169} normal megakaryocyte
{13745} megakaryocyte
{25191} hematocele (guy got kicked probably)
{39557} hemorrhage into renal pelvis (this was a TTP case)
{05938} purpura from thrombocytopenia

Category index
Great hematology image collection

Nice photos

Platelet production
Ed Lulo's Pathology Gallery

Large cell in the center
KU Collection

Rare Bleeding Disorder Database
Group from Italy

American Society of Hematology (?!)
Image Bank
For the gung-ho students

KCUMB Students
"Big Robbins" -- RBC / Bleeding
Lectures follow Textbook



Vessel severed

Plasma contacts Tissue Factor (TF) on cell surfaces
("the procoagulant response")

TF binds VII/VIIa

VII/VIIa complex with TF activates IX and X

And the rest happens
like in your old textbooks.

All diseases of inadequate hemostasis have spontaneous bleeding (petechiae, purpura, mucous membranes, GI bleeding, hematuria, into joint spaces, or even just unusually heavy periods -- the endometrium can be ablated for this (Am. J. Ob. Gyn. 202: 348.e1-7, 2010) and/or excessive bleeding after trauma or surgery.

The range is from lethal diseases (factor VIII:C deficiency, Bernard-Soulier's, Glanzmann's) to non-diseases (factor XII deficiency, many von Willebrand's).

Three groups:

THE WHOLE BUSINESS OF HEMOSTASIS IS FULL OF PITFALLS. Missing von Willebrand's disease (and missing it is very, very common) may get a parent sent to prison on a bogus charge of child abuse. Failing to manage anticoagulation or component therapy meticulously can cause deadly thrombosis or catastrophic post-surgical bleeding. Missing a slightly prolonged PT before surgery, or a slightly long INR on a "stable" patient taking warfarin, or not knowing exactly what to do when you DO spot these, are all very common malpractice nightmares.


{14727} finger-stick blood; platelets clumped!

{14117} bleeding time, step 1
{14120} bleeding time, step 2
{14123} bleeding time, step 3
{14126} bleeding time, step 4
{14129} bleeding time, step 5
{14132} bleeding time, step 6
{14135} bleeding time, step 7
{14138} bleeding time, step 8
{14141} bleeding time, step 9
{14144} bleeding time, step 10

INCREASED VASCULAR FRAGILITY ("nonthrombocytopenic purpuras", etc.): bleeding problems despite normal platelet count, bleeding time, PT, aPTT, TT, FDP)

{05940} scurvy, gums
{38195} scurvy case, bone

{12261} erythema multiforme case with purpura
{12262} erythema multiforme case with purpura
{12529} erythema multiforme case with purpura

REDUCED PLATELET NUMBER ("THROMBOCYTOPENIA"): Ped. Clin. N.A. 51: 1109, 2004, lots more

{11526} hemorrhage in thrombocytopenia (* "Sweet's syndrome" case)

{13805} giant platelets, myelofibrosis case


{24786} essential thrombocythemia
{13748} "megakaryocytic myelosis"

ABNORMALITIES IN COAGULATION FACTORS (abnormal PT, aPTT, TT, and/or FDP; usually normal platelet count and bleeding time)


CLASSIC HEMOPHILIA ("factor VIII deficiency", hemophilia A, "royal blood"): Review of the two major hemophilias: Lancet 379: 1447, 2007; BMJ 344: e2707, 2012.

    Sex-linked recessive deficiency of factor VIII:C (gene F8).

    This is a mild, moderate, or severe bleeding disorder affecting 1 in every 5000 men.

      Female carriers may have mild disease due to unlucky lyonization (Blood 85: 599, 1995).

      Severe cases have maybe 1% or less activity of the healthy protein.

Queen Victoria carried IX deficiency
Queen Victoria actually carried IX deficiency

Large hemorrhage
KU Collection

VON WILLEBRAND'S DISEASE ("pseudohemophilia")

FACTOR IX DEFICIENCY (hemophilia B, Christmas disease)



HYPERCOAGULABLE BLOOD: "Thrombophilia"; "hypercoagulopathy". Not rare, but tends to get overlooked. Big reviews: Am. J. Med. 116: 81, 2004; Ann. Int. Med. 138: 128, 2003; Postgrad. Med. 101(5): 249, May 1997. Lab screening: update Am. J. Clin. Path. 126: 120, 2006, Am. J. Clin. Path. 137: 553, 2012, and J. Clin. Path. 59: 156, 2006 (nobody really knows what to order or when to order it).

DISSEMINATED INTRAVASCULAR COAGULATION ("DIC", defibrination syndrome; "Death Is Coming")

DIC in a baby, etc.
Caused by Hib
Vaccine information


WebPath Photo

Schistocytes, no platelets
Wikimedia Commons

{03178} DIC, kidney, gross with hemorrhages
{03180} DIC, glomerulus, with fibrin-platelet thrombi
{03189} DIC, petechiae on heart
{03192} DIC, liver with recent infarcts
{09629} DIC, fibrin-platelet thrombus in brain
{39649} DIC, fibrin-platelet thrombi
{39817} schistocytes
{13895} schistocytes
{12237} Kasabach-Merritt syndrome patient


The coagulation system, with factors, platelets, and vessels, is a chaotic one -- especially, it's probably impossible to predict the effects of large numbers of medications on ICU patients, who famously develop bleeding disorders and/or hypercoagulability (Crit. Care Med. 38(S6): S198, 2010).


A few of the early Christian writers argued that the earth could not be round. They used several fallacies, most famously that people on the other side would fall off and that there would be nothing to hold it up. These writers claimed that all non-Christian thought was deeply flawed and led to immorality and the world's evils. The great church leader Augustine, who is probably best-known today for his "Confessions", urged these people to stop. Every informed person knew they were wrong -- ludicrously so -- and they were discrediting the Christian faith.

During the middle ages, Anselm, one of the archbishops of Canterbury, came up with the "ontological argument" to prove the existence of God. By definition nothing can be better than God, existing is better than not existing, so God must exist. I doubt that many people have ever found this very persuasive. Some of Anselm's own contemporaries didn't, and Anselm replied graciously to those who disagreed.

From what I have read and heard, the clotting cascade is the centerpiece of today's most-often-cited proof of the existence of God. The claim that every portion of the clotting cascade is finely-tuned to work together was popularized by Michael Behe, the only "intelligent design" advocate at the national level with bona fide scientific credentials. (I refuse to recognize the one other guy, whose scientific training was sponsored -- with the intent that he would write creationist books -- by a cult that has taught that its founder conceived his eight children by blowing in his wife's ear. The other three major players are all law-school types, who are professionally trained to argue positions even when they know they are wrong. The mathematician also refused at the last minute to testify.) Unlike Archbishop Anselm, the intelligent design proponents (though superficially polite) accuse their opponents of the vilest motives and of rank stupidity.

Real scientists will recognize the old creationist fallacy, "How could A evolve without B, and how could B evolve without A?" Of course, things evolve together. And Behe's claim that the coagulation cascade is "irreducibly complex" is indisputably false. The evolution of the clotting cascade is well-documented, and as Darwin's theory predicts, it seems to give the same phylogenetic tree as classic comparative anatomy. (If this really failed for even a single protein or gene, Darwin's theory would be refuted and "intelligent design" pretty much established. Are people like Behe looking? Of course not. The exceptions or can't-call cases, discovered of course by real scientists, that you'll see cited in "the ongoing debate" are obviously minor aberrations.)

Whales lack factor XII, the gene being inactivated. Turtles lack factors XI and XII. Fish lack prekallikrein, XI, and XII. Lampreys have a primitive system with tissue factor, prothrombin, and fibrinogen. Obviously the rest of the cascade developed unit by unit to modulate the primitive system. And this totally refutes the idea of "irreducible complexity." See PNAS 100: 7257, 2003. Origins of the vertebrate coagulation system: Thromb. Hemo. 89: 420, 2003 (England); Blood Cell. Mol. Dis. 29: 57, 2002. There's a review of all the vertebrate systems in J. Thromb. Hemo. 1: 1487, 2003. Conservation back to the horseshoe crab: J. Mol. Bio. 282: 459, 1998. The common origin of the clotting and complement cascades (like Darwin's finches, everything used to do something else): Trend Bioch. Sci. 27: 67, 2002. A theologically-inclined guy at Harvard reviews this in J. Thromb. Hemo. 1: 227, 2003. It is inconceivable that the "intelligent design" proponents do not know this by now, and the fact that they persist tells me a great deal about who they really are.

I wrote the above in 2003. By November 2005, the principal "intelligent design" website (the Discovery Institute, a front group for the Unification Church / Moonies) mentioned the business about clotting in lampreys, and provides a link to a page by Behe on which the data is supposedly reviewed and the argument is supposedly refuted. But the linked page doesn't even mention it. You can find it yourself. This is typical of how disinformation artists operate.

In "Kitzmiller vs. Dover" (2005), Behe admitted under oath in open court on cross-examination that he knew the blood clotting cascade argument to be false. As far as I am concerned (and the judge was concerned), this ended the "intelligent design" business. The handful of other scientists who had been named as witnesses all refused to testify. The lawyering stopped, with the losers going on to making political capital and money for ultraconservative churches by claiming to be persecuted saints. For people of science, and informed members of the public, the whole business will be remembered for what it really was -- one more disinformation campaign by pseudo-religionists. Was the motive the promotion of public virtue (i.e., the belief that people are better-behaved if they believe these sorts of lies?) Or was it just a money-maker? As a close observer, I believe the truth stands somewhere in the middle.

One objection that I have to this stuff involves disease itself, my focus. If God builds genes and living systems to order, why not make a more stable genetic system, one that would not be so subject to mutations? Every human being who suffers from hereditary disease or from cancer is a reminder of the real origin of our bodies.

To his credit, Dr. Behe acknowledged in the fine print of his book, "The Edge of Evolution", that all living creatures have a common descent ("common ancestry of chimps and humans... Despite some remaining puzzles, there's no reason to doubt that Darwin had this point right, that all creatures on earth are biological relatives." Remember he's the only creationist to go under oath lately.

If you are involved with this "intelligent design / creationism" stuff, please stop. If you (like me) are a person of faith, you should demand that people stop spreading lies as "proof of the existence of God." I find nothing "spiritual" or "moral" about wholesale breaking of the ninth commandment. The Christian Bible compares our present "animal bodies" to our future state as spiritual beings. Like Job, I prefer to stand in awe and not demand answers to everything right now. I expect you do, too.

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Teaching Pathology

Pathological Chess

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